Total Folate Intake Research Articles

Serum Unmetabolized Folic Acid: The Straw That Broke Dihydrofolate Reductase’s Back? ,

Serum Unmetabolized Folic Acid: The Straw That Broke Dihydrofolate Reductase’s Back? ,

Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults1–4

AbstractBackground: Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid–fortified foods or supplements.Objectives: We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid–containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L.Methods: Serum samples from the cross-sectional NHANES 2007–2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC–tandem mass spectrometry.Results: In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L.Conclusions: UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.

Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.

Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

Abstract 15588: Dietary Choline and Betaine Intakes are Associated with Incident Cardiovascular Disease Events and Left Ventricular Mass: The Jackson Heart Study

Introduction: Acute choline deficiency in rodent models causes lipid accumulation in liver, heart and arterial tissues. Alternatively, some studies reported an association between increased blood concentrations of total choline and cardiovascular disease. Several mechanisms have been described through which dietary intake of choline and its derivative betaine may be associated with subclinical atherosclerosis. Thus, we assessed the association between these two essential nutrients and cardiovascular risk. Methods: We analyzed data on food frequency questionnaire and baseline visit measurements on 3,924 Jackson Heart Study African American participants. Multivariable linear regression models were used to assess the association between choline and betaine intake with carotid intima-media thickness, coronary artery calcium, abdominal aortic calcium, and left ventricular mass. Cox proportional hazards regression models were used to calculate associations between choline and betaine intake with time to incident coronary heart disease (CHD) and stroke. Results: During an average seven years of follow-up, 129 incident CHD events and 100 incident stroke events were documented. Greater choline intake was associated with lower left ventricular mass (p = 0.0006 for trend across the choline quartiles, in women). After adjusting for cardiovascular disease risk factors including age, BMI, smoking, systolic blood pressure, fasting plasma glucose, plasma creatinine, cholesterol fractions, plasma homocysteine and dietary variables (intake of total energy, alcohol, folate, methionine, vitamins B6 and B12), choline intake appeared to be protective against incident stroke in men, HR = 0.19 (0.04, 0.82), when comparing the third quartile of intake to the lowest quartile of intake. In women, unexpectedly, participants in the third quartile of betaine intake showed an increased risk of incident CHD, relative to the lowest quartile, HR = 2.06 (1.02, 4.18). Conclusion: Higher dietary choline intake was associated with decreased left ventricular mass in both men and women, and appeared to be protective against incident stroke among men. The observation of greater risk of incident CHD with higher betaine intake among women requires further investigation.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

BackgroundHealth authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy with the risk of spontaneous preterm delivery (PTD).MethodsThe Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 66,014 women with singleton pregnancies resulting in live births in 2002–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,755).ResultsThe median total folate intake was 313 μg/d (interquartile range IQR 167–558) in the overall population and 530 μg/d (IQR 355–636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.ConclusionsOur findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-014-0375-1) contains supplementary material, which is available to authorized users.

Dietary one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms: results of the Netherlands cohort study.

Previous epidemiologic research suggests a protective role of one-carbon nutrients in carcinogenesis. Folate, however, may play a dual role in neoplasms development: protect early in carcinogenesis and promote carcinogenesis at a later stage. We prospectively examined associations between intake of total folate, methionine, riboflavin, vitamin B6, and risk of lymphoid and myeloid neoplasms (including subtypes) and investigated whether alcohol modified the effects of folate. The Netherlands Cohort Study consists of 120,852 individuals who completed a baseline questionnaire in 1986, including a 150-item food-frequency questionnaire. After 17.3 years of follow-up, 1,280 cases of lymphoid and 222 cases of myeloid neoplasms were available for analysis. Intakes of folate, methionine, and riboflavin were not associated with lymphoid or myeloid neoplasms. For vitamin B6, a statistically significantly increased myeloid neoplasms risk was observed (highest vs. lowest quintile: HR = 1.87; 95% confidence intervals, 1.08-3.25). When analyzing by lymphoid and myeloid neoplasms subtypes, no clear associations were observed for most subtypes, with just a few increased risks for some subtypes and nutrients. Some risks became nonsignificant after excluding early cases. No interaction between alcohol and folate was observed. We observed a few significant positive associations; however, some of these would be expected to arise due to chance alone. Furthermore, some risks became nonsignificant after excluding early cases. Therefore, we conclude that there is no association between one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms. This study contributes substantially to the limited and inconclusive evidence on the association with one-carbon nutrients.

Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

A Free New Dietary Supplement Label Database for Registered Dietitian Nutritionists

The Academy of Nutrition and Dietetics recognizes the importance of including dietary supplements (DS) in assessing and planning dietary intakes. 1 Position of the American Dietetic AssociationNutrient Supplementation. J Am Diet Assoc. 2009; 109: 2073-2085 Abstract Full Text Full Text PDF PubMed Google Scholar DS use in the United States has increased markedly during the past 30 years and is now widespread across all segments of society. 2 Briefel R. Johnson C.L. Secular trends in dietary intake in the United States. Ann Rev Nutr. 2004; 24: 401-431 Crossref PubMed Scopus (478) Google Scholar , 3 Radimer K.L. Bindewald B. Hughes J. Ervin B. Swanson C. Picciano M.F. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004; 160: 339-349 Crossref PubMed Scopus (647) Google Scholar , 4 Picciano M.F. Dwyer J.T. Radimer K.L. et al. Dietary supplement use among infants, children, and adolescents in the United States, 1999-2002. Arch Pediatr Adolesc Med. 2007; 161: 978-985 Crossref PubMed Scopus (116) Google Scholar , 5 Bailey R.L. Gahche J.J. Lentino C.V. et al. Dietary supplement use in the United States, 2003-2006. J Nutr. 2011; 141: 261-266 Crossref PubMed Scopus (585) Google Scholar , 6 Gahche J, Bailey R, Burt V, et al. Dietary supplement use among US adults has increased since NHANES III (1988-1994). NCHS Data Brief, No. 61. US Department of Health and Human Services. April 2011. Google Scholar At present, more than half of adults and a third of US children have used one or more DS within the past 30 days, with multivitamin, multimineral (MVMM) products especially common. 7 Dwyer J. Nahin R.L. Rogers G.T. et al. Prevalence and predicators of children's dietary supplement use: The 2007 National Health Interview Survey. Am J Clin Nutr. 2013; 97: 1331-1337 Crossref PubMed Scopus (67) Google Scholar , 8 Bailey R.L. Fulgoni V.L. Keast D.R. Lentino C.V. Dwyer J.T. Do dietary supplements improve micronutrient sufficiency in children and adolescents?. J Pediatr. 2012; 161: 837-842 Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar Because supplements are now major sources of several nutrients, such as calcium and vitamin D, in American diets, it is important for registered dietitian nutritionists (RDNs) to include their contributions when assessing intakes or planning diets. 9 Fulgoni V.L. Keast D.R. Bailey R.L. Dwyer J.T. Foods, fortificants and supplements: where do Americans get their nutrients?. J Nutr. 2011; 141: 1847-1854 Crossref PubMed Scopus (339) Google Scholar , 10 Bailey R.L. Fulgoni V.L. Keast D.R. Dwyer J. Dietary supplement use is associated with higher intakes of minerals from food sources. Am J Clin Nutr. 2011; 94: 1376-1381 Crossref PubMed Scopus (120) Google Scholar , 11 Bailey R.L. Fulgoni V.L. Keast D.R. Dwyer J.T. Examination of vitamin intakes among US adults by dietary supplement use. J Acad Nutr Diet. 2012; 112: 657-663 Abstract Full Text PDF PubMed Scopus (109) Google Scholar Likewise, for national nutrition surveillance, the contributions to nutrient intakes from supplements must be considered to identify groups at dietary risk because their intakes decrease below the estimated average requirement (EAR) or above the upper tolerable intake level. 12 Dwyer J. Picciano M.F. Raiten D.J. Estimation of usual intakes: What we eat in America–NHANES. J Nutr. 2003; 133: 609S-623S Crossref PubMed Google Scholar For example, when supplements are included in assessments, the proportion of the US population that is below the EAR is much less for several vitamins 11 Bailey R.L. Fulgoni V.L. Keast D.R. Dwyer J.T. Examination of vitamin intakes among US adults by dietary supplement use. J Acad Nutr Diet. 2012; 112: 657-663 Abstract Full Text PDF PubMed Scopus (109) Google Scholar and fewer women are “at risk” (defined as below the EAR) for folate intake than when they are not. 13 Bailey R.L. Dodd K.W. Gahche J.J. et al. Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-2006. Am J Clin Nutr. 2010; 91: 231-237 Crossref PubMed Scopus (185) Google Scholar , 14 Branum A.M. Bailey R. Singer B.J. Dietary supplement use and folate status during pregnancy in the United States. J Nutr. 2013; 143: 486-492 Crossref PubMed Scopus (102) Google Scholar For some nutrients, like folic acid, the upper tolerable intake level is established based solely for the form that comes from fortificants in foods and in dietary supplements. RDNs, epidemiologists, and public health officials also need accurate dietary supplement databases to evaluate possible associations between nutrient intake and disease outcomes.

Food-group and nutrient-density intakes by Hispanic and Latino backgrounds in the Hispanic Community Health Study/Study of Latinos

Hispanics are a heterogeneous group of individuals with a variation in dietary habits that is reflective of their cultural heritage and country of origin. It is important to identify differences in their dietary habits because it has been well established that nutrition contributes substantially to the burden of preventable diseases and early deaths in the United States. We estimated the distribution of usual intakes (of both food groups and nutrients) by Hispanic and Latino backgrounds by using National Cancer Institute methodology. The Hispanic Community Health Study/Study of Latinos is a population-based cohort study that recruited participants who were 18-74 y of age from 4 US cities in 2008-2011 (Miami, Bronx, Chicago, and San Diego). Participants who provided at least one 24-h dietary recall and completed a food propensity questionnaire (n = 13,285) were included in the analyses. Results were adjusted for age, sex, field center, weekend, sequencing, and typical amount of intake. Overall, Cubans (n = 2128) had higher intakes of total energy, macronutrients (including all subtypes of fat), and alcohol than those of other groups. Mexicans (n = 5371) had higher intakes of vitamin C, calcium, and fiber. Lowest intakes of total energy, macronutrients, folate, iron, and calcium were reported by Dominicans (n = 1217), whereas Puerto Ricans (n = 2176) had lowest intakes of vitamin C and fiber. Food-group servings reflected nutrient intakes, with Cubans having higher intakes of refined grains, vegetables, red meat, and fats and Dominicans having higher intakes of fruit and poultry, whereas Puerto Ricans had lowest intakes of fruit and vegetables. Central and South Americans (n = 1468 and 925, respectively) were characterized by being second in their reported intakes of fruit and poultry and the highest in fish intake in comparison with other groups. Variations in diet noted in this study, with additional analysis, may help explain diet-related differences in health outcomes observed in Hispanics and Latinos.

Folate intake and the risk of prostate cancer: a systematic review and meta-analysis.

There is conflicting evidence regarding the role of folate on the risk of developing prostate cancer. We performed a systematic review and quantitative meta-analysis of folate blood levels and folate intake, and the risk of prostate cancer. Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 11 October 2013, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of prostate cancer. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a random effects model. The dietary folate meta-analysis comprising 11 studies with 15 336 cases and a total sample size of 146 782 found no statistically significant association with prostate cancer, with an OR of 0.97 (95% CI 0.89-1.06). The total folate meta-analysis comprising of 5 studies with 7114 cases and a total sample size of 93 781 also found no statistically significant association with prostate cancer, with an OR of 0.99 (95% CI 0.82-1.19). The blood folate meta-analysis comprising of seven studies with 6122 cases and a total sample size of 10 232 found an increased risk of prostate cancer with high blood folate levels, with an OR of 1.43 (95% CI 1.06-1.93). There was significant heterogeneity (I(2)=79.5%, P<0.01). Removal of an outlier study removed the heterogeneity (I(2)=0.0%, P=0.54) and the association remained significant with an OR of 1.14 (95% CI 1.02-1.28). Dietary and total folate intake do not appear to be significantly associated with the risk of prostate cancer. High blood folate levels are associated with an increased risk of prostate cancer. These conclusions are limited by the predominance of included studies originating from developed countries with mostly Caucasian populations. Further research in populations with a high prevalence of non-Caucasian backgrounds is needed.

A Prospective Study of Folate, Vitamin B6, and Vitamin B12Intake in Relation to Exfoliation Glaucoma or Suspected Exfoliation Glaucoma

Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma. To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk. National prospective cohort study using more than 20 years of follow-up data from the Nurses' Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses' Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78,980 Nurses' Health Study women and 41,221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%). Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires. Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis. Vitamin B₆ and vitamin B₁₂ intake was not associated with EG/SEG risk in pooled analyses (P = .52 and P = .99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 μg/d) was 0.75 (95% CI, 0.54-1.04; P = .02 for linear trend). These results were not materially altered after adjustment for vitamin B₆ and vitamin B₁₂ intake. An association was observed for supplemental folate intake but not for dietary folate only (P = .03 and P = .64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P = .06 for linear trend). Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.

Folate intake and the risk of breast cancer: a systematic review and meta-analysis.

There is conflicting epidemiological evidence on the role of folate and breast cancer risk. We conducted a systematic review and quantitative meta-analysis of folate intake and folate blood levels and the risk of breast cancer. Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched to April 11, 2014, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of breast cancer. The meta-analysis of dietary folate intake comprising 36 studies with 34,602 cases, and a total sample size of 608,265 showed a decreased risk of breast cancer, with an odds ratio (OR) of 0.84 [95% confidence interval (CI) 0.77-0.91]. When stratified by menopausal status and by study design, none of the meta-analyses of prospective studies showed any statistically significant decrease in the risk of breast cancer. The meta-analysis of total folate showed no statistically significant association with breast cancer OR of 0.98 (95% CI 0.91-1.07). There was no significant association between either dietary or total folate intake and breast cancer when stratified by hormonal receptor status. The meta-analysis of blood folate levels found no significant association with the risk of breast cancer, with an OR of 0.86 (95% CI 0.60-1.25). Breast cancer does not appear to be associated with folate intake, and this did not vary by menopausal status or hormonal receptor status. Folate blood levels also do not appear to be associated with breast cancer risk.

Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility

Folic acid supplements are commonly used by infertile women which leads to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to IVF pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P<0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P<0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.Folate is one of the B vitamins which has been suggested to be related to infertility. Folic acid is an artificial form of folate which is commonly used in dietary supplements. Folic acid supplementation has been shown to increase folate concentrations and decrease concentrations of the amino acid homocysteine in the blood. Folic acid supplementation is commonly used by infertile women, but the effect on pregnancy outcome in women with a diagnosis of unexplained infertility has not been thoroughly investigated. In the present study, folic acid supplement use and folate status (concentrations of folate and homocysteine) in women with unexplained infertility were evaluated in relation to pregnancy outcome. In addition, the use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile control women. Our results showed that women with unexplained infertility used considerably more folic acid supplements and had higher total folic acid intake from supplements compared with fertile control women. Women with unexplained infertility had better blood folate and homocysteine concentrations than fertile women, but folic acid supplementation or folate status were not related to pregnancy outcome following the infertility treatment. In conclusion, high folic acid intake or good folate status did not increase the possibility of a birth of a healthy baby after infertility treatment in women with unexplained infertility.

Critical evaluation of lowering the recommended dietary intake of folate

We evaluated the recommendation of the Austrian, German, and Swiss Societies for Nutrition of lowering dietary folate intake from 400 to 300 μg dietary folate equivalents/d. A dose-response relation exists between folate intake or plasma level and disease risk within the normal range. Improving folate status can prevent between 30% and 75% of neural tube defects. A prepregnancy plasma folate of >18.0 nmol/L (mean 26.1 nmol/L) is associated with low total homocysteine (tHcy) (<10.0 μmol/L) and optimal prevention of birth defects. Because the closure of the neural tube occurs in the first 8 weeks after conception, women with low prepregnancy folate intake cannot achieve maximal risk reduction. The Austrian, German, and Swiss Societies for Nutrition recommend that young women should additionally supplement with 400 μg folic acid at least 4 weeks before conception. This short time window is not sufficient to achieve optimal plasma folate and tHcy levels in the majority of women. Factors affecting the relation between folate intake and blood biomarkers are total folate intake, baseline plasma folate, time available for supplement use, dose and form (folic acid or methyl folate), genetic polymorphisms, physiological and lifestyle factors. Lowering the recommended dietary folate intake may have important public health consequences. Elderly people and young women are at risk for diseases related to folate shortage. Reducing birth defects through supplementation of folic acid remains a poor option, as <20% of young women (i.e., in Germany) supplement with the vitamin. Recommending adequate food folate intake is crucial for reaching the target protective plasma folate levels in the population.

Dietary Intake Status among Korean Female Breast Cancer Survivors

Objectives: We aimed to evaluate dietary intake among female breast cancer survivors in a cross-sectional study. Methods: A total of 127 women who had breast cancer surgery at least 6 months before baseline were included. Dietary intake of female breast cancer survivors was assessed through self-reported 3 day-dietary records. To compare dietary intake between breast cancer survivors and general female population without cancer, we selected the 1:4 age matched women from the 2011 Korean National Health and Nutrition Examination Survey (KNHANES). In the KNHANES, participants were asked about their dietary intake using the 24-hour dietary recalls. We also examined whether dietary intake varied by age group, cancer stage, or time since surgery among breast cancer survivors. We used the generalized linear model to compare their dietary intakes. Results: Intakes of total energy, beta-carotene, folate, vitamin C, plant iron and fruits were lower among breast cancer survivors with longer time since surgery compared to those with shorter time (p < 0.05). Breast cancer patients with higher stage at diagnosis tended to consume less legumes (p = 0.01) than those with lower stage. When we compared dietary intake between breast cancer survivors and the general female population without cancer, breast cancer survivors were more likely to consume most of macro- and micro-nutrients in larger quantity (p < 0.05) and adhere to healthier diet characterized by higher intakes of legumes, seed and nuts, vegetables and fishes and shells than the general female population who never had been diagnosed with cancer (p < 0.05). Conclusions: Our study results suggested that the intakes of nutrients and foods varied by time since surgery and cancer stage among breast cancer survivors and dietary intakes among breast cancer survivors differed from that in the general population. Further prospective studies are warranted to explore the association between dietary intakes of specific food items and survival among Korean breast cancer survivors. Korean J Community Nutr 19(2): 163~175, 2014

High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study

Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid. The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants. This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake. The inadequacy of vitamin B-12 intake (<1.2 μg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample. These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.

Impact of Folate Intake on Prostate Cancer Recurrence Following Definitive Therapy: Data from CaPSURE™

A randomized, placebo controlled clinical trial of folic acid supplementation for the chemoprevention of colorectal adenoma revealed an increased incidence of prostate cancer in the treatment group. Limited data exist on postdiagnostic folate/folic acid intake and the risk of prostate cancer progression. We prospectively examined the association between postdiagnostic folate consumption and the risk of prostate cancer recurrence after radical prostatectomy, external beam radiation therapy and brachytherapy. This study was done in 1,153 men treated with radical prostatectomy, external beam radiation therapy and brachytherapy who had clinical stage T1-T2c prostate adenocarcinoma and participated in the CaPSURE Diet and Lifestyle substudy by completing the semiquantitative Food Frequency Questionnaire in 2004 to 2005. We used Cox proportional hazards regression to analyze the association between folate intake and prostate cancer progression. Prostate cancer progressed in 101 men (8.76%) during a mean 34-month followup. After multivariate adjustment we observed no evidence of an association of the intake of total folate, dietary folate or dietary folate equivalents with prostate cancer recurrence. On secondary analysis by treatment after radical prostatectomy patients in the lowest decile of dietary folate intake had a 2.6-fold increase in the risk of recurrence (HR 2.56, 95% CI 1.23-5.29, p = 0.01). In patients treated with external beam radiation and brachytherapy we observed no evidence of an association between prostate cancer progression and increased folate intake. Results suggest that the consumption of foods and multivitamins that contain folate is not associated with prostate cancer progression after definitive treatment.

Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated. We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 μg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10. We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller. CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population.

Retracted: Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

BackgroundHealth authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD).MethodsThe Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628).ResultsThe median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.ConclusionsOur findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Abstract 4811: Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition.

Abstract Background: Pancreatic cancer (PC) has an exceptionally high mortality rate due to late discovery and poor prognosis. The etiology of the cancer is largely unknown and primary prevention strategies are limited for this lethal cancer. Over the past years, evidence has been accumulated for folate which may play a role in carcinogenesis. Previous epidemiological studies, however, have shown inconsistent results in relation to PC risk with a weak inverse association with folate intake from foods, but not from supplements. The recent large study from the Pooling Project found no association between folate intake and PC risk. However, in the pooled analysis, folate data may be heterogeneous across studies and countries, thus not readily comparable. In the EPIC study, we obtained dietary folate intake data that was standardized across 10 participating countries using the EPIC Nutrient DataBase. Folic acid fortification or supplementation use was not common in Europe at the baseline data collection. We then set out to evaluate the association between total dietary folate intake and PC risk. Methods: A total of 477,245 participants without any history of cancer and with complete dietary folate information ascertained by food frequency questionnaire were followed up for 11 years, during which 904 first incident primary PC cases were recorded. Folate intake was energy-adjusted by using the residual method. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: In multivariable analyses stratified by age, sex, study center and adjusted for smoking status, energy intake, BMI, educational level, diabetes status, supplement use and dietary fiber intake, we observed non-significantly decreased PC risk with higher folate intake: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest quartile (&amp;lt;240 μg/d) was 0.65 (95% CI: 0.37, 1.13; Ptrend = 0.13). There was a borderline significant and positive trend in PC risk across folate quartiles among current smokers (HR=1.53 (0.59-3.97) for 240-291 μg/d, 3.51 (1.04-11.90) for 291-353 μg/d, and 3.31 (0.71-15.40) for ≥353 μg/d of folate intake, respectively (Ptrend = 0.07)). A similar pattern was shown when a single reference category was chosen and joint effects were determined for tertiles of folate in combination with smoking categories in relation to PC risk. When very low (&amp;lt;150 μg/d) or high intake (≥500 μg/d) were investigated using 200-300 μg/d as a reference, we found a slightly increased, but statistically non-significant risk estimate with a very low intake (HR=1.28, 95% CI: 0.40-4.06). Conclusions: We found non-significant inverse associations between dietary folate intake and PC risk in the large European study. There was some evidence that the findings were heterogeneous by smoking status. Our results warrant further investigation. Citation Format: Jin Young Park, H.B(as) Bueno-de-Mesquita, Pietro Ferrari, Paolo Vineis, Elisabete Weiderpass, Nadia Slimani, for the EPIC Study Group. Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2013-4811