Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians

Modeling Demonstrates That Folic Acid Fortification of Whole-Wheat Flour Could Reduce the Prevalence of Folate Inadequacy in Canadian Whole-Wheat Consumers ,

Risk Assessment of Folic Acid in Food Supplements

Fortification of bakery and corn masa–based foods in Mexico and dietary intake of folic acid and folate in Mexican national survey data

The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 µg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003–2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19–39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 µg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL.

Background: The Institute of Medicine set a tolerable upper intake level (UL) for usual daily total folic acid intake (1,000 µg). Less than 3% of US adults currently exceed the UL.Objective: The objective of this study was to determine if folic acid fortification of corn masa flour would increase the percentage of the US population who exceed the UL.Design: We used dietary intake data from NHANES 2001–2008 to estimate the percentage of adults and children who would exceed the UL if corn masa flour were fortified at 140 µg of folic acid/100 g.Results: In 2001–2008, 2.5% of the US adult population (aged≥19 years) exceeded the UL, which could increase to 2.6% if fortification of corn masa flour occurred. With corn masa flour fortification, percentage point increases were small and not statistically significant for US adults exceeding the UL regardless of supplement use, sex, race/ethnicity, or age. Children aged 1–8 years, specifically supplement users, were the most likely to exceed their age-specific UL. With fortification of corn masa flour, there were no statistically significant increases in the percentage of US children who were exceeding their age-specific UL, and the percentage point increases were small.Conclusions: Our results suggest that fortification of corn masa flour would not significantly increase the percentage of individuals who would exceed the UL. Supplement use was the main factor related to exceeding the UL with or without fortification of corn masa flour and within all strata of sex, race/ethnicity, and age group.

A Comparison of Micronutrient Inadequacy and Risk of High Micronutrient Intakes among Vitamin and Mineral Supplement Users and Nonusers in Canada 3

Effect of folic acid on human trophoblast health and function in vitro

Focused Revision: Policy statement on folic acid and neural tube defects

Fruit, Vegetables, and Folate: Cultivating the Evidence for Cancer Prevention

Gestational Folate and Folic Acid Intake among Women in Canada at Higher Risk of Pre-Eclampsia.

To estimate vitamin intakes and assess the contribution of different food groups to vitamin intakes in adults aged 18-64 years in Ireland as estimated in the North/South Ireland Food Consumption Survey. Intakes are reported for retinol, carotene, total vitamin A, vitamin D, vitamin E, thiamin, riboflavin, pre-formed niacin, total niacin equivalents, vitamin B6, vitamin B12, folate, biotin, pantothenate and vitamin C. The adequacy of vitamin intakes in the population and the risk of occurrence of excessive vitamin intakes are also assessed. Food consumption was estimated using a 7-day food diary for a representative sample (n=1379; 662 men and 717 women) of 18-64-year-old adults in the Republic of Ireland and Northern Ireland selected randomly from the electoral register. Vitamin intakes were estimated using tables of food composition. In general, the percentage of the population with vitamin intakes below the average requirement (AR) was low. Mean daily intake of total vitamin A was below the AR in 20.2% and 16.6% of men and women, respectively, and mean daily intake of riboflavin was below the AR in 12.5% and 20.6% of men and women, respectively. Mean daily folate intakes were below the AR for folate in 11.2% and 6.6% of women aged 18-35 years and 36-50 years, respectively. Only 2.2% of women aged 18-35 years and 5.2% of women aged 36-50 years achieved the recommended folate intake of 600 microg day(-1) for women of reproductive age for the prevention of neural tube defects. A high proportion of the population has a low dietary vitamin D intake and is largely dependent on sunlight exposure to maintain adequate vitamin D status. Except for pre-formed niacin, the 95th percentile intake of vitamins did not exceed the tolerable upper intake level (UL) for any group and was much less than the UL for most vitamins. Although 20.8% of men and 6.3% of women exceeded the UL for pre-formed niacin (which is 35 mg, based on nicotinic-acid-induced flushing), the large contribution of meat and fish to the intake of niacin (as nicotinamide) suggests that the risk of overexposure to nicotinic acid is much lower than this and is probably solely related to supplement use. A small proportion of men (4.0%) and women (1.2%) aged 51-64 years had retinol intakes that exceeded the UL (3000 microg) and while the 95th percentile intake of women in the 18-50 year age group was well below the UL, 1.5% of 18-35-year-old and 2.4% of 36-50-year-old women had mean daily retinol intakes above the UL. About 2.0% of women had intakes of vitamin B6 that exceeded the UL (25 mg). There were significant differences by age and sex in nutrient densities of vitamin intakes between men and women and between age groups, which may be explained by differences in consumption of particular food groups as well as different patterns of supplement use. Nutritional adequacy of the population for most vitamins was good. Folate intake in women of childbearing age is not meeting current recommendations for the prevention of neural tube defects. The public health significance of the relatively high proportion of men and women with inadequate intakes of vitamin A and riboflavin and with low dietary intakes of vitamin D is unclear and should be investigated further. With the possible exception of niacin (flushing) and vitamin B6 (neuropathy), there appears to be little risk of the occurrence of adverse effects due to excessive consumption of vitamins in this population, based on current dietary practices.

Background: Higher folate intake has been reported to be associated with modestly lower risk of colorectal cancer, but the overall state of the evidence is inconclusive. Revisiting putative and established lifestyle-related risk factors from the perspective of intertumoral heterogeneity is warranted, as risk relationships for a molecular subtype may be attenuated toward the null when colorectal cancer is investigated as a single disease. Aim: To investigate folate and folic acid intakes in relation to the risk of molecular subtypes of colorectal cancer. Methods: We pooled individual-level observational data from 7542 colorectal cancer cases and 7066 controls within the collaborative framework of the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR). Odds ratios per sex- and study-specific quartile increase in dietary and total folate intake, and for folic acid supplement use (yes/no), were estimated using logistic regression for case-only analyses and multinomial models for case-control analyses. Minimally adjusted analyses included sex, age, study and total energy intake as covariates. Tumor marker variables included microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. Results: In case-only analyses, we observed no heterogeneity in associations between folate intake, with or without supplemental folic acid (taking into consideration folic acid fortification when relevant), or with folic acid supplement use, and the risk of any subtype of colorectal cancer based on individual molecular tumor markers (lowest p for heterogeneity 0.073). In case-control analyses, higher dietary and total folate intake and folic acid supplement use were associated with a lower risk of most molecular tumor subtypes (all odds ratios were below one, and most were statistically significant). Adjustment for a larger set of potential confounders had no material effect on risk estimates. Conclusion: In this large, pooled analysis, higher dietary and total folate intakes and folic acid supplement use were all associated with a lower risk of colorectal cancer, regardless of individual molecular tumor markers including MSI status, CIMP, and BRAF and KRAS mutations. Citation Format: Bethany Van Guelpen, Björn Gylling, Sophia Harlid, Anna Winkvist, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Steven J. Gallinger, Graham G. Giles, Marc J. Gunter, Michael Hoffmeister, Li Hsu, Mark A. Jenkins, Roger L. Milne, Polly A. Newcomb, Shuji Ogino, John D. Potter, Conghui Qu, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Mikael O. Woods, Tabitha A. Harrison, Ulrike Peters. Folate and folic acid intake in relation to molecular subtypes of colorectal cancer; a pooled analysis of 7542 cases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2355.

Folic acid source, usual intake, and folate and vitamin B-12 status in US adults: National Health and Nutrition Examination Survey (NHANES) 2003–2006

Contributions of enriched cereal-grain products, ready-to-eat cereals, and supplements to folic acid and vitamin B-12 usual intake and folate and vitamin B-12 status in US children: National Health and Nutrition Examination Survey (NHANES), 2003–2006

ABSTRACTFollowing a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)‐5‐methyltetrahydrofolic acid glucosamine and l‐5‐methyltetrahydrofolic acid calcium salts), namely risk of cobalamin‐dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin‐deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose–response between folic acid intake and resolution of megaloblastic anaemia in cobalamin‐deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1–3 years, 300 μg/day for 4–6 years, 400 μg/day for 7–10 years, 600 μg/day for 11–14 years and 800 μg/day for 15–17 years. A UL of 200 μg/day is established for infants aged 4–11 months. The ULs apply to the combined intake of folic acid, (6S)‐5‐methyltetrahydrofolic acid glucosamine and l‐5‐methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5‐methyl‐tetrahydrofolic acid salts.