Low Dietary Folate Intake Research Articles

Association between dietary folate intake and bone mineral density in a diverse population: a cross-sectional study

BackgroundOsteoporosis is a major public health problem, yet the association between dietary folate intake and bone health has been rarely studied. This study aimed to investigate the relationship between dietary folate intake and bone mineral density (BMD) in the general population of the USA.MethodsUtilizing data from the National Health and Nutrition Examination Survey, dietary folate intake was gauged through 24-h dietary recall and BMD was determined via dual-energy X-ray absorptiometry. Multivariate linear regression models and generalized additive models were employed for correlation analysis.ResultsThe study incorporated 9839 participants (48.88% males, aged 20–85 years, mean age: 47.62 ± 16.22). The average dietary folate intake stood at 401.1 ± 207.9 μg/day. And the average total femur, femoral neck, trochanter, intertrochanter, and lumbar BMD were 0.98 ± 0.16 g/cm2, 0.84 ± 0.15 g/cm2, 0.73 ± 0.13 g/cm2, 1.16 ± 0.19 g/cm2, and 1.03 ± 0.15 g/cm2, respectively. The higher quartiles of dietary folate intake directly correlated with increased total femoral, femoral neck, intertrochanteric, and lumbar BMD (P for trend = 0.003, 0.016, < 0.001, and 0.033, respectively). A consistent positive association between folate intake and BMD across age groups was observed, with significant findings for individuals over 80 years and non-Hispanic whites. Physical activity level and serum 25-hydroxyvitamin D levels influenced the association, with an optimal daily folate intake of 528–569 µg recommended for postmenopausal women.ConclusionIn summary, our study reveals a significant positive association between dietary folate intake and BMD, across different age groups and particularly among individuals over 80 years old. Non-Hispanic whites benefit the most from increased folate intake. Physical activity level and serum 25-hydroxyvitamin D levels interact with this association. Screening and early intervention for osteoporosis may be essential for individuals with low dietary folate intake.

Tolerability of capecitabine in difference racial/ethnic groups.

e18833 Background: Capecitabine (cap) is an oral chemotherapy agent used for treatment of solid malignancies. The recommended dose of cap generally ranges from 1000mg/m2 to 1250mg/m2 twice daily, but many patients require a dose reduction during treatment due to AE. It is unclear whether patients of different race have better tolerability of cap than others. In Asian populations for example, potential differences in tolerance have been attributed to low dietary folate intake. Race is a social construct; however it has been used to identify groups of patients within a population. We aimed to understand the tolerability of cap among patients of different racial/ethnic groups. Methods: In this retrospective chart review, we studied patients treated with cap at Tufts Medicine (three centers in MA, USA) between 2017-2021. Patients treated with cap alone, concurrent with other chemo, or concurrent with radiation for solid tumors were included. Patients were excluded if race/ethnicity data was not available. We collected demographic information, cap dose, AE, and dose reductions during the treatment period. Dose intensity (DI) was calculated (Total administered cap dose during treatment period (mg)/Recommended cap dose (mg/m2) * BSA (m2)). ANOVA was used to determine difference between groups. Results: 202 patients were included: 134 (66.3%) White, 35 (17.3%) Asian, 22 (10.9%) African American/Black, and 11 (5.4%) other race. 10 (5%) identified as Hispanic ethnicity. Most common cancer types treated were 46 (22.8%) breast, 44 (21.8%) colon, and 39 (19.3%) rectal. Average DI by race/ethnicity is outlined in Table 1. There was no statistically significant difference in DI among patients of different racial groups (p = 0.232). AEs leading to dose reduction or cap discontinuation occurred in 93 (46%) of patients, the most common outlined in Table 1. Conclusions: We found no significant difference in cap DI or toxicity among patients of different racial groups. The study is limited by the small sample size and that it is retrospective. The patients presented are racially diverse but live in one geographic area, which could impact environmental factors such as dietary folate intake. Our findings suggest that there is no difference in tolerated DI among all patients. Clinicians should not empirically reduce the dose of cap based on race and should assess tolerance on an individual basis. [Table: see text]

Dietary nutrient intake related to higher grade cervical intraepithelial neoplasia risk: a Chinese population-based study

BackgroundDietary nutrient intake plays a significant role in carcinogenesis. Few studies have investigated the association between dietary nutrient intake and cervical intraepithelial neoplasia (CIN) risk in China.MethodsData on 2304 women from an ongoing cohort comprising 40,000 women from China in 2014 were included. Study randomly selected 218 out of 2304 people as subjects during 2019. All participants were surveyed through in-person interviews, physical examinations, and laboratory tests. Clinical data were obtained from physical examinations and laboratory tests. Dietary intakes were assessed using a semiquantitative food frequency questionnaire. Nutrition intakes from 26 food sources were calculated using a comprehensive validated database. Descriptive statistics were used to describe the frequency and proportion, and mean and standard deviation of the demographic characteristics. Characteristics were examined for significant differences, and Pearson chi-square tests were used for categoric variables. Logistic regression was used to obtain odds ratios (ORs) and confidence intervals (CIs) for CIN risk in each nutrient intake quartile relative to that in the highest quartile.ResultsThe food frequency questionnaire exhibited acceptable reproducibility and reasonable validity in assessing nutrient intakes among these women. After adjusting for multiple confounders, several dietary nutrients showed significant associations with CIN2+ risk. Low dietary folate intake was associated with the risk of CIN2+ (first versus fourth quartile: OR = 1.55, 95% CI 1.03–2.33). Similar results were also observed for vitamin B6 (OR = 1.63, 95% CI 1.08–2.46), vitamin C (OR = 1.59, 95% CI 1.05–2.42), niacin (OR = 1.65, 95% CI 1.08–2.51), and vitamin K (second versus fourth quartile: OR = 1.60, 95% CI 1.05–2.44).ConclusionsLow folate; vitamin B6, C, and K; and niacin intakes were associated with CIN2+ risk. Nutrients may influence the development of higher grade CIN and cervical cancer.Trial registration The study was registered in the Chinese Clinical Trial Register (ChiCTR-ROC-15006479) (https://www.chictr.org.cn).

Relationship of obesity with B vitamin status: analysis of NDNS data from UK women of reproductive age

AbstractPre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an effect not explained by lower dietary folate intake, or non-use of folic acid supplements (as recommended globally to women before and in early pregnancy for NTD prevention). While the exact mechanism linking NTD and obesity is poorly understood, it is possible that a compromised status or metabolism of folate and/or of the closely related micronutrients (vitamin B12, B6 and riboflavin) may be involved. To date however, this hypothesis has not been adequately explored. This study therefore aimed to investigate the relationship of obesity with folate and related B vitamin biomarkers in a representative cohort of non-pregnant UK women of reproductive age. Data were accessed from the most recent UK National Diet and Nutrition Survey (NDNS; Years 7–8; 2015–16), a rolling cross-sectional survey designed to gather information from a representative sample of the UK population on nutrient intakes, food consumption and nutritional status. Data for women aged 16–45 years (non B vitamin supplement users; n 364), were extracted on: anthropometry (height, weight, body mass index [BMI] and waist circumference [WC]), dietary intakes of B vitamins and biomarkers for serum and red blood cell folate, vitamin B12 (total serum B12 and holotranscobalamin), vitamin B6 (plasma pyridoxal-5-phosphate [PLP]) and riboflavin (erythrocyte glutathione reductase activation coefficient EGRAac]). Prevalence of overweight and obesity (i.e. BMI: 25–30kg/m2 and &gt; 30kg/m2) was 28% and 22% respectively, whilst abdominal obesity (i.e. WC &gt; 88cm) was present in 31% of the women. Total serum B12 (r -0.215, P 0.012) and PLP (r -0.270, P 0.002) were negatively correlated with WC, with similar, albeit weaker, correlations found for BMI. Correspondingly, women with abdominal obesity compared to those without, had a lower status of total serum B12 (Median values of: 212 v 249 v pmol/L; P 0.049), B6 (31.5 v 40.5 nmol/L; P 0.002) and EGRac (1.43 v 1.36; P 0.031). No differences in B vitamin dietary intake were observed by categories of abdominal obesity. Abdominal obesity may be a risk factor for low status of both vitamins B12 and B6, independently of dietary intake. Further investigation to elucidate the potential underlying mechanism is warranted. These findings also highlight the importance of taking abdominal obesity into account, in addition to BMI, when examining possible adverse impacts of obesity on micronutrient status.

Association of Intake Folate and Related Gene Polymorphisms with Breast Cancer.

Breast cancer is one of the most common malignancies in women worldwide and is associated with a variety of risk factors. Folate and vitamin B12 are key elements of the one-carbon metabolism pathway where methylenetetrahydrofolate reductase (MTHFR) plays a significant role. Though many molecular and epidemiological studies have been performed to explore the relationship between intake folate, vitamin B12, MTHFR gene polymorphism and breast cancer risk, there is no consensus to date. By reviewing the relevant literatures and summarizing the potential effect of dietary folate intake on MTHFR genes polymorphism and breast cancer risk, we conclude that MTHFR C677T gene polymorphism is associated with breast cancer risk among Asian, but not Caucasians, and the MTHFR A1298C gene polymorphism is not a susceptibility factor of breast cancers. Concomitant low activity of MTHFR enzyme resulted from C677T gene polymorphism and low dietary folate intake is associated with increased breast cancer risk.

Associations of food insecurity and psychosocial measures with diet quality in adults aging with HIV

ABSTRACTPeople aging with HIV face social stressors which may negatively affect their overall nutrition. Here, we assess relationships between self-reported measures of depression, perceived stress, social support, and food insecurity with diet quality in older adults with HIV. A retrospective analysis of self-reported data from parent study at The University of Alabama at Birmingham 1917 HIV Clinic was performed. The study sample consisted of sixty people living with HIV (PLWH) with controlled HIV infection (<50 copies/mL), aged 50 years or older who participated in a cross-sectional microbiome study. Dietary intake was measured using the NHANES 12-month Food Frequency Questionnaire (FFQ) and three Automated Self-Administered (ASA) 24-hr diet recalls to calculate diet quality scores using the Mediterranean Diet Score (MDS); alternative Healthy Eating Index (aHEI); and the Recommended Food Score (RFS) indices. Food insecurity was measured with the Food Security Questionnaire (FSQ). Participants completed the following psychosocial scales: (1) depression – Patient Health Questionnaire-8 (PHQ8); (2) perceived stress – Perceived Stress Scale (PSS-10); (3) social support – Multidimensional Scale of Perceived Social Support (MSPSS). Linear regression models were used to investigate relationships among variables controlling for gender and income. The cohort was characterized as follows: Mean age 56 ± 4.6 years, 80% African-American, and 32% women. Mean body mass index (BMI) was 28.4 ± 7.2 with 55% reporting food insecurity. Most participants reported having post-secondary education (53%), although 77% reported annual incomes <$20,000. Food insecurity was independently associated with measures of poor dietary intake: aHEI (β = −0.08, p = .02) and MDS (β = −0.23, p < 0.01) and with low dietary intake of fibre (β = −0.27, p = .04), vitamin E (β = −0.35, p = .01), folate (β = −0.31, p = .02), magnesium (β = −0.34, p = .01) and copper (β = −0.36, p = .01). These data indicate food insecurity is associated with poor diet quality among PLWH. Clinical interventions are needed to improve food access for PLWH of low SES.

LOXL1 Polymorphisms: Genetic Biomarkers that Presage Environmental Determinants of Exfoliation Syndrome.

An agnostic high throughput search of the genome revealed a robust association between LOXL1 genetic polymorphisms and exfoliation syndrome (XFS), a discovery that likely would not have been possible with candidate or family-based gene search strategies. While questions remain regarding how LOXL1 gene variants contribute to XFS pathogenesis, it is clear that the frequencies of disease-related alleles do not track with the varying disease burden throughout the world, prompting a search for environmental risk factors. A geo-medicine approach revealed that disease load seemed to increase as a function of the distance from the equator. The exact reason for this extraequatorial disease distribution pattern remains unclear, but a greater amount of time spent outdoors is a robust risk factor for XFS, suggesting climatic factors such as ocular solar exposure and colder ambient temperature may be involved in disease pathogenesis. Prospective studies have also implicated higher coffee consumption and lower dietary folate intake in association with incident XFS. The discovery of environmental risk factors for XFS suggests that preventive measures may help to reduce ocular morbidity from XFS.

Association between Total Folate Intakes and Depression amongst Three Racial/Ethnic Groups

Low dietary folate intake has been associated with depression outcomes, but few studies have been reported on the association in diverse populations. Using data from the National Health and Nutrition Examination Survey (NHANES), we examined the relationship between depression and folate intake from diet and supplementation in non-Hispanic whites, Hispanics and African Americans. 3,687 adult respondents from the 2009-2010 NHANES cycle were included. Statistical methods for analyzing data from complex survey sample designs were used to assess differences by race/ethnicity in demographic, behavioral, dietary and depression variables and to assess the relationship between depression and folate, adjusting for confounding variables using multivariable logistic regression. We observed significant (p < 0.01) differences by race/ethnicity for all demographic, behavioral, dietary and depression variables, except for physical activity. The relationship between dietary folate and depression significantly differed by race/ethnicity (p = 0.03), with an inverse and significant association in Hispanics only (OR= 0.25; 95% CI= 0.09 - 0.70.; p for trend = 0.02). These data suggest that a diet high in folate, such as from dark green leafy vegetables, may be associated with a reduced odds for depression, and specifically, Hispanics may benefit from nutrition education to potentially reduce depression in the population.

Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects

Folate deficiency has been putatively implicated in the onset of diverse metabolic abnormalities, including insulin resistance, by altering epigenetic processes on key regulatory genes. The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic processes such as adiposity and glucose homeostasis. This study hypothesized associations between low folate intakes and lower methylation levels of the CAMKK2 gene, with the presence of metabolic alterations in subjects with obesity. A cross-sectional ancillary study was conducted in obese subjects (n=47) from the RESMENA study (Spain). Fat mass was measured by dual-energy x-ray absorptiometry. Dietary intake and metabolic profile were assessed by validated methods. DNA methylation and gene expression in peripheral white blood cells were analyzed by microarray approaches. A total of 51 cytosine-phosphate-guanine sites were associated with folate intake (false discovery rate values < 0.0001), including one located in the 5′ untranslated region of the CAMKK2 gene (Illumina ID, cg16942632), which was selected and separately analyzed. Subjects with total folate intake lower than 300μg/d showed more fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment–insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1 than those consuming at least or more than 300μg/d. Of note, folate deficiency was related to lower CAMKK2 methylation. Interestingly, CAMKK2 methylation negatively correlated with the HOMA-IR index. Furthermore, CAMKK2 expression directly correlated with HOMA-IR values. In summary, this study suggests associations between low folate intakes, lower CAMKK2 gene methylation, and insulin resistance in obese individuals.

Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Variants, Folate Intake, and Susceptibility to Breast Cancer

Context: Breast cancer is the most common cancer among women, worldwide. Both genetic and environmental factors are involved in the risk of breast cancer. Folate is an essential nutrient that is involved in DNA synthesis, repair, and methylation. Single nucleotide polymorphisms (SNPs) in folate related genes, such as methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are suitable candidates for investigation the role of these variants in susceptibility to breast cancer. Evidence Acquisition: Using the relevant English language studies from the search engines, such as MEDLINE/PubMed, EMBASE, and Scopus from 2005 to 2016, the present review looks at the role of MTHFR C677T and A1298C variants, synergism between these gene variants along with folate intake in susceptibility to breast cancer. Results: It seems the MTHFR C677T polymorphism is associated with the risk of breast cancer among Asians but not in Caucasians. However, the MTHFR A1298C polymorphism might not be a susceptibility factor for breast cancer. The MTHFR haplotypes alone or along with low dietary intake of folate were not involved in susceptibility to breast cancer. Conclusions: Association between MTHFR C677T polymorphism with the risk of breast cancer could be attributed to the lower activity of the MTHFR enzyme in the presence of 677T allele with reduced availability of folate that may result in uracil misincorporation in the DNA and cancer development. The absence of establishment of a role for MTHFR haplotypes and a synergism between low dietary intake of folate along with MTHFR polymorphisms in susceptibility to breast cancer might be due to differences in allelic frequency of MTHFR variants in various populations, stage of cancer, the familial and early onset cancer, and the influence of environmental factors. To establish the role of MTHFR haplotypes in relation to folate intake in susceptibility to breast cancer, more studies with adequate sample size that investigate the role of MTHFR gene polymorphisms along with dietary intake of folate in the risk of breast cancer are necessary.

Maternal folic acid supplementation and dietary folate intake and congenital heart defects.

BackgroundIt has been reported that folic acid supplementation before and/or during pregnancy could reduce the risk of congenital heart defects (CHDs). However, the results from limited epidemiologic studies have been inconclusive. We investigated the associations between maternal folic acid supplementation, dietary folate intake, and the risk of CHDs.MethodsA birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. After exclusion of stillbirths and multiple births, a total of 94 births were identified with congenital heart defects, and 9,993 births without any birth defects. Unconditional logistic regression was used to estimate the associations.ResultsCompared to non-users, folic acid supplement users before pregnancy had a reduced risk of overall CHDs (OR: 0.42, 95% CI: 0.21–0.86, Ptrend = 0.025) after adjusted for potential confounders. A protective effect was observed for certain subtypes of CHDs (OR: 0.37, 95% CI: 0.16–0.85 for malformation of great arteries; 0.26, 0.10–0.68 for malformation of cardiac septa; 0.34, 0.13–0.93 for Atrial septal defect). A similar protective effect was also seen for multiple CHDs (OR: 0.49, 95% CI: 0.26–0.93, Ptrend = 0.004). Compared with the middle quartiles of dietary folate intake, lower dietary folate intake (<149.88 μg/day) during pregnancy were associated with increased risk of overall CHDs (OR: 1.63, 95% CI: 1.01–2.62) and patent ductus arteriosus (OR: 1.85, 95% CI: 1.03–3.32). Women who were non-user folic acid supplement and lower dietary folate intake have almost 2-fold increased CHDs risk in their offspring.ConclusionsOur study suggested that folic acid supplementation before pregnancy was associated with a reduced risk of CHDs, lower dietary folate intake during pregnancy was associated with increased risk. The observed associations varied by CHD subtypes. A synergistic effect of dietary folate intake and folic acid supplementation was also observed.

Epidemiology and Molecular Biology of Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cancer and the second most common cause of cancer-related death in the United States. Nonmodifiable risk factors include age, male sex, African-American ethnicity, and personal or family history of CRC or polyps (especially if these were diagnosed at a younger age), inflammatory bowel disease, or diabetes. Modifiable risk factors include poor physical activity; obesity; high consumption of red meats, processed meats, or alcohol; low total dietary intake of fiber, folate, fruits, or vegetables; and smoking tobacco. There have been several advances in diagnostic techniques, which, when combined with newly discovered genetic pathways, contribute to an expanding knowledge on which to base treatment. There are three known major molecular pathways of CRC carcinogenesis: the chromosomal instability pathway, the microsatellite instability pathway, and the serrated carcinoma pathway. Approximately 5% of all CRC cases will have a specific known genetic mutation associated with a well-characterized familial cancer syndrome with defined features. These syndromes are important to recognize distinctly as their identification facilitates surveillance and management with the aim of prevention, prophylaxis, and surgical cure. This review contains 2 figures, 3 tables and 50 references. Key words: colon cancer, colorectal cancer, familial, familial adenomatous polyposis, Lynch syndrome, microsatellite, polyp, polyposis, rectal cancer, serrated

Epidemiology and Molecular Biology of Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cancer and the second most common cause of cancer-related death in the United States. Nonmodifiable risk factors include age, male sex, African-American ethnicity, and personal or family history of CRC or polyps (especially if these were diagnosed at a younger age), inflammatory bowel disease, or diabetes. Modifiable risk factors include poor physical activity; obesity; high consumption of red meats, processed meats, or alcohol; low total dietary intake of fiber, folate, fruits, or vegetables; and smoking tobacco. There have been several advances in diagnostic techniques, which, when combined with newly discovered genetic pathways, contribute to an expanding knowledge on which to base treatment. There are three known major molecular pathways of CRC carcinogenesis: the chromosomal instability pathway, the microsatellite instability pathway, and the serrated carcinoma pathway. Approximately 5% of all CRC cases will have a specific known genetic mutation associated with a well-characterized familial cancer syndrome with defined features. These syndromes are important to recognize distinctly as their identification facilitates surveillance and management with the aim of prevention, prophylaxis, and surgical cure. This review contains 2 figures, 3 tables and 50 references. Key words: colon cancer, colorectal cancer, familial, familial adenomatous polyposis, Lynch syndrome, microsatellite, polyp, polyposis, rectal cancer, serrated

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

Aberrations in one-carbon metabolism were reported to increase breast cancer risk by influencing the DNA synthesis and methylation of DNA and catecholamines. However, the results of these association studies remain inconclusive. We have explored the contribution of eight genetic polymorphisms in modulating the susceptibility to breast cancer by performing a meta-analysis of worldwide studies. In total, 62 case-control studies representing 17 different populations involving 18,117 breast cancer cases and 23,573 healthy controls were included in this meta-analysis. Out of the eight polymorphisms analyzed, methylenetetrahydrofolate reductase (MTHFR) C677T exhibited positive association with the breast cancer risk in both fixed effects (OR 1.14, 95% CI 1.10-1.17) and random effects (OR 1.10, 95% CI 1.02-1.18) models. Solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A exhibited positive association (OR 1.16, 95% CI 1.03-1.31) while MTR A2756G exhibited an inverse association (OR 0.78, 95% CI 0.75-0.82) with the breast in fixed effect model alone. Significant heterogeneity was observed in the association of MTHFR C677T with breast cancer even between studies from the same geographical area, specifically among Chinese, Indians, and Turks. Subgroup analysis revealed MTHFR C677T-mediated breast cancer risk in post-menopausal women and women with low dietary intake of folate. Geographical area wise segregation of data revealed MTHFR-mediated increased breast cancer risk in populations who consume methionine-rich diet. Altitude-level variations were observed in the association of SHMT1 C1420T with breast cancer. India and Brazil of same altitude showed an inverse association with this polymorphism, while USA and China that share similar altitude showed a null association. MTHFR C677T and SLC19A1 G80A are the two polymorphisms of one-carbon metabolic pathway that increase breast cancer in the worldwide population. Dietary patterns and altitudinal variations are the likely risk modulators that are contributing toward ethnic- and population-level variations in genetic associations.

Plasma homocysteine and folate levels and dietary folate intake in adolescents and young adults who underwent kidney transplantation during childhood

Hyperhomocysteinemia (hyper-Hcy) is an important and reversible cardiovascular disease risk factor. We examined the prevalence of hyper-Hcy, plasma folate levels, and dietary folate intake in adolescents and young adults who had undergone kidney transplantation during childhood to assess the necessity for managing dietary folate. This cross-sectional study was performed in 89 kidney transplant recipients (age at kidney transplantation: 12.6 ± 4.1 years; age during study: 21.2 ± 5.5 years). Hyper-Hcy and plasma folate deficiency were defined as plasma homocysteine (Hcy) >15 nmol/ml and plasma folate <3.0 ng/ml, respectively. Of the patients, 60 (67.4 %) had hyper-Hcy and 14 (15.7 %) had plasma folate deficiency. Plasma homocysteine levels correlated negatively with estimated glomerular filtration rate (eGFR; r = -0.565, p < 0.01) and plasma folate levels (r = -0.434, p < 0.01). For determinants of plasma homocysteine levels, a priori selected variables included kind of calcineurin inhibitor, age at kidney transplantation, pretransplant duration of dialysis, time since transplantation, age at examination, eGFR, and plasma folate. Stepwise multiple linear regression analysis revealed eGFR and plasma folate levels as significant independent variables influencing plasma homocysteine levels. Dietary folate intake in 11 of 16 patients (66.8 %) with eGFR ≥ 60 ml/min/1.73 m(2) was below the recommended dietary allowance for Japanese. The prevalence of hyper-Hcy and plasma folate deficiency, as well as the low dietary folate intake, suggest that dietary management of folate is necessary for adolescents and young adults who have undergone kidney transplantation during childhood.

Dietary Intake of Folate, B-Vitamins and Methionine and Breast Cancer Risk among Hispanic and Non-Hispanic White Women

BackgroundLow dietary folate intake is associated with several neoplasias, but reports are inconsistent for breast cancer. Additionally, the association of folate with breast cancer estrogen receptor (ER) status is not well established.ObjectiveTo determine if dietary intakes of folate, B-vitamins (B2, B6, B12) and methionine are associated with breast cancer risk and ER status in Hispanic, and non-Hispanic White women in the southwestern US.Materials and MethodsPrimary breast cancer cases (n = 2,325) in the 4-Corners region (Arizona, Colorado, New Mexico and Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls (n = 2,525) were frequency-matched by ethnicity and age (±5 years). Dietary intake, physical activity and other exposures were assessed using in-person interviews. Risk was assessed through multivariable and multinomial logistic regression with adjustment for relevant covariates.ResultWhile there was no overall association with breast cancer, the highest quartile of folate intake was marginally inversely associated with ER− breast cancer (Odds Ratio (OR) = 0.50, 95%CI 0.25–1.00, p for trend = 0.07). Vitamin B12 intake was inversely associated with breast cancer also (OR = 0.73, 95%CI 0.53–1.00, p for trend = 0.06), particularly for the highest quartile of ER+ breast cancer (OR = 0.67, 95%CI 0.46–0.99, p for trend = 0.06), among NHW women (OR = 0.49, 95%CI 0.29–0.81, p for trend = 0.01) and invasive breast cancer (OR = 0.63; 95%CI: 0.42, 0.93, P trend = 0.01). Methionine intake was also inversely associated with ER+ breast cancer (OR for 4th quartile = 0.83, 95%CI 0.66–1.03, p for trend = 0.04), primarily among Hispanic women (OR = 0.71, 95%CI 0.47–1.06, and P for trend = 0.02).ConclusionHigher intake of folate is marginally associated with a lower risk for ER− breast cancer, and higher intakes of vitamin B-12 and methionine are marginally associated with a lower risk of ER+ breast cancer.

Folate Deficiency Is Associated With Oxidative Stress, Increased Blood Pressure, and Insulin Resistance in Spontaneously Hypertensive Rats

The role of folate deficiency and associated hyperhomocysteinemia in the pathogenesis of metabolic syndrome is not fully established. In the current study, we analyzed the role of folate deficiency in pathogenesis of the metabolic syndrome in the spontaneously hypertensive rat (SHR). Metabolic and hemodynamic traits were assessed in SHR/Ola rats fed either folate-deficient or control diet for 4 weeks starting at the age of 3 months. Compared to SHRs fed a folate-replete diet, SHRs fed a folate-deficient diet showed significantly reduced serum folate (104 ± 5 vs. 11 ± 1 nmol/L, P < 0.0005) and urinary folate excretion (4.3 ± 0.6 vs. 1.2 ± 0.1 nmol/16 h, P < 0.0005) together with a near 3-fold increase in plasma total homocysteine concentration (4.5 ± 0.1 vs 13.1 ± 0.7 μmol/L, P < 0.0005), ectopic fat accumulation in liver, and impaired glucose tolerance. Folate deficiency also increased systolic blood pressure by approximately 15 mm Hg (P < 0.01). In addition, the low-folate diet was accompanied by significantly reduced activity of antioxidant enzymes and increased concentrations of lipoperoxidation products in liver, renal cortex, and heart. These findings demonstrate that the SHR model is susceptible to the adverse metabolic and hemodynamic effects of low dietary intake of folate. The results are consistent with the hypothesis that folate deficiency can promote oxidative stress and multiple features of the metabolic syndrome that are associated with increased risk for diabetes and cardiovascular disease.

Proportion of neural tube defects attributable to known risk factors

Recognized risk factors for neural tube defects (NTDs) poorly predict population-level NTD risk. However, the proportion of NTDs that can be attributed to these risk factors is uncertain. To determine the proportion of NTD cases that is attributable to known or suspected risk factors (i.e., female infant sex, family history of NTDs, and maternal Hispanic ethnicity, obesity, pregestational diabetes, gestational diabetes, low dietary folate intake, lack of folic acid supplementation, anticonvulsant use, and hot tub or sauna use), we estimated the adjusted population attributable fraction (aAF) for each factor, using the method of Eide and Geffler and data from the National Birth Defects Prevention Study. Our analyses of these data indicate that the proportion of cases of spina bifida and anencephaly that can be attributed to known risk factors is 28% and 44%, respectively. For spina bifida, the factor with the greatest attributable fraction was maternal obesity (aAF, 10%), whereas for anencephaly it was Hispanic ethnicity (aAF, 15%). Our analyses indicate that known risk factors account for <50% of NTD cases. Hence, the majority of NTD cases are attributable to, as yet, unidentified factors. These findings highlight the need for continued research to identify genetic and additional nongenetic risk factors for NTDs. Further, these findings suggest that strategies that aim to reduce the risk of NTDs associated with maternal Hispanic ethnicity and obesity may have the greatest impact on the population prevalence of these conditions.

The role of nutrition and body composition in peripheral arterial disease

Peripheral arterial disease (PAD) has not been as extensively investigated as other cardiovascular diseases. However, the available data suggest that nutrition-based treatment strategies have the potential to reduce the cost-economic burden of PAD substantially. Abdominal obesity is associated with PAD and prospective and cross-sectional studies have shown that a low dietary intake of folate and reduced synthesis of vitamin D are associated with an increased risk of PAD and severe walking impairment in patients who have the disease. However, dietary patterns that are associated with decreased cardiovascular risk might protect against PAD. A small number of clinical trials have provided evidence that increased intakes of niacin and insoluble fiber might be associated with decreased levels of LDL cholesterol and thrombogenic biomarkers, as well as increased serum levels of HDL cholesterol in patients with PAD. However, little evidence that antioxidants, vitamins B(6) and B(12), or essential fatty acid supplements improve clinical outcomes in these patients exists. Overall, data on the effects of nutrition, body composition, and nutritional supplementation on the risk, progression, and prognosis of PAD are scarce. Further research into these areas is required to allow the development of evidence-based nutritional guidelines for the prevention and treatment of the disease.

Dietary Intake and Serum Levels Status of Folate and Vitamin B12 among Jordanian Colorectal Cancer Patients: a case‐control study

Low daily dietary intakes of folate and vitamin B12 have been associated with an increased risk of colorectal cancer in animal and human studies. The retrospective dietary intake of folate and vitamin B12 was investigated as well as the biochemical measurements of these nutrients in colorectal cancer patients and controls group in Jordan. Four hundred and forty subjects were recruited for this case‐control study, 220 colorectal cancer patients and 220 controls. The mean daily intake of folate and vitamin B12 was significantly lower amongst patients (189.2 ± 11.7 μg/day and 1.09 ± 1.1 μg/day respectively) when compared to the controls group (212.5 ± 13.1 μg/day and 1.49 ± 1.3 μg/day respectively). The same pattern was observed for folate serum measurements of colorectal cancer patients (6.6 ± 0.3 μg/L) as compared to controls (16.2 ± 2.8 μg/L) and for serum vitamin B12 of cases (233.7±17.9 pg/mL) as compared to controls group (458.9±30.9 pg/mL). This study suggests that the studied colorectal cancer patients had a low dietary intake of folate and vitamin B12 that is concomitant with low serum levels of these two nutrients, a well established etiological factor for different types of human cancer, including colorectal cancer.