Intake Of Synthetic Folic Acid Research Articles

Total folate, natural folate and synthetic folic acid intake associations with adult depressive symptoms.

In the United States, synthetic folic acid has become an important source of folate in the era of mandatory folic acid fortification. This study aimed to evaluate the associations between total folate, natural folate and synthetic folic acid intakes and depressive symptoms among US adults. Cross-sectional data was collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Dietary data were obtained through two 24-h dietary recall interviews. Depressive symptoms were detected by PHQ-9 (Patient Health Questionnaire-9), participants whose depression scores over 10 points were diagnosed as depressive symptoms. Weighted logistic regressions were used to analyze the associations between different forms of folate and depressive symptoms. Among 19244 participants included in this study, 9.2% of them met the definition of depressive symptoms. In fully adjusted models, total folate intake and natural folate intake were inversely associated with depressive symptoms respectively, while synthetic folic acid was not. The multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of depressive symptoms were 0.69 (0.54-0.89), 0.51 (0.39-0.68) for the highest versus lowest quartile of total folate and natural folate intake, respectively. We also found two L-shaped dose-response curves among total folate intake, natural folate intake with depressive symptoms, respectively. Total folate intake, natural folate intake may be inversely associated with depressive symptoms among US adults, while the association was not significant between synthetic folic acid and depressive symptoms.

Abstract 2239: Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study

Abstract Background: Cancer patients are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine, and may promote cancer growth, especially among those with neoplastic alterations. Objective: We investigated the prospective association between synthetic versus natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. Design: In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 years, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (95% CI). Results: Synthetic folic acid intake was positively associated with risk of recurrence among NMIBC patients (medium vs. low intake: HR=1.72; 95% CI=1.20, 2.48; P=0.003; high vs. low intake: HR=1.80; 95% CI=1.14, 2.84; P=0.01). Patients with higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium/high vs. low: OR=2.08; 95% CI=1.08, 4.02; P=0.03). In contrast, natural folate intake tended to be inversely associated with risk of progression (medium/high vs. low: HR=0.68; 95% CI=0.44, 1.04; P=0.08). Conclusions: High intake of synthetic folic acid, in contrast to the natural forms, is associated with increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, suggesting that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation regarding folate intake among NMIBC patients. Citation Format: Huakang Tu, Colin P. Dinney, Yuanqing Ye, Barton H. Grossman, Seth P. Lerner, Xifeng Wu. Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2239.

Is folic acid safe for non–muscle-invasive bladder cancer patients? An evidence-based cohort study

Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine and may promote cancer growth, especially among those with neoplastic alterations. We investigated the prospective association between synthetic compared with natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food-frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 y, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted HRs and ORs with 95% CIs. Synthetic folic acid intake was positively associated with a risk of recurrence among NMIBC patients (medium compared with low intake-HR: 1.72; 95% CI: 1.20, 2.48; P = 0.003; high compared with low intake-HR: 1.80; 95% CI: 1.14, 2.84; P = 0.01). Patients with a higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium or high compared with low-OR: 2.08; 95% CI: 1.08, 4.02; P = 0.03). In contrast, natural folate intake tended to be inversely associated with the risk of progression (medium or high compared with low-HR: 0.68; 95% CI: 0.44, 1.04; P = 0.08). A high intake of synthetic folic acid, in contrast to the natural forms, is associated with an increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, which suggests that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation with regard to folate intake among NMIBC patients.

Reduced plasma homocysteine levels in elderly Australians following mandatory folic acid fortification – A comparison of two cross-sectional cohorts

ObjectiveIn 2009, Australia implemented mandatory folic acid fortification in wheat flour for bread-making. The primary aim was to improve folate status in reproductive-aged women to reduce neural tube defect incidence. However, folic acid consumption has consequently increased in all demographics. Blood folate is inversely associated with homocysteine levels, a risk factor for multiple diseases. Therefore, we assessed the impact of mandatory folic acid fortification on homocysteine levels in elderly Australians. MethodsHomocysteine and blood folate levels were compared between two elderly cross-sectional cohorts (pre-versus post-mandatory folic acid fortification). Importantly, dietary habits were assessed to evaluate the confounding influence of altered dietary patterns not related to fortification. ResultsPost-fortification, plasma homocysteine levels (10.6 vs. 14.5 μmol/L) and hyperhomocysteinemia incidence (27.2% vs 56.3%) were significantly reduced, relative to the pre-fortification subjects. This was associated with increased blood folate (red cell: 1243 vs 1066 nmol/L, serum 28.0 vs 23.9 nmol/L), and increased intake of synthetic folic acid (366.8 vs 231.0 DFE/day) but not natural folate (332.7 vs 323.6 DFE/day). Limited other differences were detected in dietary intake patterns between groups. The positive relationship between homocysteine levels and age was abrogated post-fortification (p = 0.3 vs p = 0.0003). ConclusionsA potential off-target benefit of mandatory folic acid fortification in Australia was demonstrated. With many countries still considering the merits and consequences of mandatory fortification policies, it is important to unravel the off-target effects including dietary context.

Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.

Folate is absorbed across the colon of adults: evidence from cecal infusion of 13C-labeled [6S]-5-formyltetrahydrofolic acid

Background:Folate deficiency increases the risk of several human diseases. Likewise, high intakes of folate, particularly synthetic folic acid intake, may be associated with adverse health outcomes in humans. A more comprehensive understanding of the “input side” of folate nutrition may help to set dietary recommendations that strike the right balance between health benefits and risks. It is well known that the microflora in the colon produce large quantities of folate that approach or exceed recommended dietary intakes; however, there is no direct evidence of the bioavailability of this pool in humans. Objective:The objective was to determine whether, and to what extent, the natural folate vitamer 5-formyltetrahydrofolic acid is absorbed across the intact colon of humans. Design:During screening colonoscopy, 684 nmol (320μg) [13C]glutamyl-5-formyltetrahydrofolic acid was infused directly into the cecum of 6 healthy adults. Three or more weeks later, each subject received an intravenous injection of the same compound (172 nmol). Blood samples were collected before and after each treatment. The ratio of labeled to unlabeled folates was determined in plasma by tandem mass spectrometry. Results:The apparent rate of folate absorption across the colon of a bolus dose of [13C]5-formyltetrahydrofolic acid infused into the cecum was 0.6 ± 0.2 nmol/h, as determined by the appearance of [13C5]5-methyltetrahydrofolic acid in plasma. In comparison, the rate of appearance of [13C5]5-methyltetrahydrofolic acid after an intravenous injection of [13C5]5-formyltetrahydrofolate was 7 ± 1.2 nmol/h. Conclusion:Physiologic doses of natural folate are absorbed across the intact colon in humans.

Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements

BackgroundMany lactating women in North America are exposed to high synthetic folic acid intakes because of food fortification and vitamin supplement use. Few data exist on the potential long-term effect of high folic acid intakes on milk folate concentrations, whereas no data are available on the effect of supplemental [6S]-5-methyltetrahydrofolate ([6S]-5-methylTHF). ObjectiveThe aim of the present study was to investigate the effect of 3 treatments (placebo, folic acid, and [6S]-5-methylTHF) on milk folate and folate-binding protein (FBP) concentrations and to determine whether unmetabolized folic acid is present in milk. DesignIn this 16-wk randomized, placebo-controlled intervention, 69 lactating women were randomly assigned to receive [6S]-5-methylTHF (416 μg/d, 906 nmol/d) or a placebo, or were assigned to receive folic acid (400 μg/d, 906 nmol/d) within 1 wk postpartum. Total milk folate, FBP, and unmetabolized folic acid concentrations were measured at 16 wk. ResultsUnmetabolized folic acid was detected in 96% of milk samples tested representing ≈8% of total milk folate concentrations. Total milk folate, FBP, and the proportion of unmetabolized milk folic acid did not differ between treatments; however, FBP concentrations were significantly lower than those published before mandatory folic acid fortification of the food supply. ConclusionMaternal intake of synthetic folic acid leads to the appearance of unmetabolized folic acid in milk and, seemingly, a down-regulation of milk FBP synthesis. The impact of these changes on the bioavailability of folate in infants requires further exploration.

Folate Intake and Food-Related Behaviors in Nonpregnant, Low-Income Women of Childbearing Age

Information about folate intake among low-income women of childbearing age remains limited. This report presents results from a cross-sectional study of folate intake and food-related behaviors in a sample of low-income, nonpregnant women of childbearing age in California. One hundred fifty-seven nonpregnant, low-income (≤185% federal poverty level) women of childbearing age (18 to 45 years) were evaluated for usual intake of natural food folate and synthetic folic acid, as well as specific food-related behaviors. Eighty-five percent of participants met the Recommended Dietary Allowance for folate, but only 37% met the current synthetic folic acid recommendation for reducing the risk of neural tube defects. Intake of naturally occurring food folate and intake of synthetic folic acid from supplements were positively associated with overall healthful food-related behaviors. Nutrition education that includes information about folic acid may be one way to improve folate intake and other healthful food behaviors among low-income women of childbearing age.

Low-income women in California may be at risk of inadequate folate intake

Folate plays a major role in preventing neural tube defects in the developing fetus, as well as in reducing the risks of cardiovascular disease, certain types of cancer and some mental health problems. We assessed the folate intakes of socioeconomically disadvantaged women of childbearing age participating in California's Food Stamp Nutrition Education program. Of 195 women studied, 59% failed to meet the Institute of Medicine's folate intake recommendations for women capable of becoming pregnant. We found significant differences among the ethnic groups studied: 45% of Hispanic, 65% of white and 77% of black women did not meet the recommendation for synthetic folic acid intake. This study supports the need for developing targeted nutrition-education lessons focusing on the importance of adequate folate consumption.