Folate fortification: potential impact on folate intake in an older population

OBJECTIVE: To examine the potential impact of different models of folate fortification of Australian foods on the folate intakes of older Australians. DESIGN: Dietary data were collected using a food frequency questionnaire from people attending a population-based health study. SETTING: Two postcode areas west of Sydney, Australia. SUBJECTS: A total of 2895 people aged over 49 y, obtained from a door knock census (79% of 3654 subjects examined). MAIN OUTCOME MEASURES: The folate intake in this population was estimated using four different models: (1) pre-fortification folate values; (2) current voluntary folate fortification in Australia; (3) universal fortification of all foods permitted to add folate, at 25% recommended dietary intake (RDI) per reference serve; and (4) universal fortification of all foods permitted to add folate, at 50% RDI per reference serve. The increased bioavailability of synthetic folic acid (SFA) was included in the analysis. RESULTS: At current voluntary folate fortification, approximately 65% of this population consume 320 microg dietary folate equivalents (DFE) or more per day from diet and supplements, and 0.4% (n=10) consume greater than the recommended upper safety level of 1000 microg from SFA. More than 95% of this older population would be expected to consume more than 320 microg DFE from diet and supplements with universal fortification at 50% of the RDI, and 0.5% (n=14) may consume greater than 1000 microg/day of SFA. CONCLUSIONS: There is unlikely to be a large increase in the proportion of older persons who are likely to consume more than the upper safety level of intake with universal folate fortification. As most of those who currently or are predicted to consume over 1000 microg SFA take supplements containing folic acid, it is highly recommended that vitamin B12 be included in any vitamin supplements containing folate. SPONSORSHIP: This study was supported by the Australian National Health and Medical Research Council (NHMRC).     

Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial

BACKGROUND: Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. OBJECTIVE: The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. DESIGN: Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). RESULTS: The consumption of fortified bread increased serum folate concentrations by 45% (mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49% (mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to 0% after 12 wk. CONCLUSION: Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.     

Promotion of folate for the prevention of neural tube defects: who benefits?

Since the publication of randomised trials showing firm evidence of prevention of neural tube defects with periconceptional folic acid, there have been population health promotion programmes to encourage women to take folic acid supplements, and the introduction of voluntary fortification of some foods with folic acid in Australia. In order to evaluate these two strategies, we collected data by self-administered questionnaire from a random sample of recently pregnant women in Western Australia between September 1997 and March 2000. Response to health promotion was measured in three ways: (1) knowledge of the association between periconceptional folate and prevention of spina bifida (the 'correct message'); (2) use of periconceptional vitamin supplements of folic acid daily in the periconceptional period; and (3) daily folate intake from fortified foods in the 6 months before pregnancy. We examined the relationship of maternal demographic and behavioural characteristics with these three measures. Overall, 62.3% of women were aware of the correct message before pregnancy, 28.5% reported taking 200 microg or more of folic acid from supplements daily in the periconceptional period and 56.6% of women obtained 100 microg or more of folic acid from fortified foods. Women who first became aware of the correct message during pregnancy or who were unaware of the correct message before or during pregnancy were more likely than women aware before pregnancy to be younger, having their first pregnancy, be single or in a de facto relationship, have no tertiary education, and be a public patient. Similar associations were seen for women taking either no folic acid or < 200 microg of folic acid in supplements daily in the periconceptional period. There were no significant associations between these demographic variables and amount of folate obtained from fortified foods. Women who were unaware of the correct message and did not take folic acid supplements were more likely to have smoked, not to have engaged in exercise, and not to have planned their pregnancy, whereas there was no association with these behavioural characteristics and intake of folate from fortified foods. These results indicate that health promotion strategies have not reached all segments of the target population equally, but there is no such disparity with folate-fortified foods, and they suggest that mandatory fortification of a staple food is likely to reach all women regardless of demographic and behavioural characteristics, and hence provide improved opportunity for prevention of neural tube defects in Australia.     

Fortification with low amounts of folic acid makes a significant difference in folate status in young women: implications for the prevention of neural tube defects.

BACKGROUND: Mandatory fortification of grain products with folic acid was introduced recently in the United States, a policy expected to result in a mean additional intake of 100 microgram/d. One way of predicting the effectiveness of this measure is to determine the effect of removing a similar amount of folic acid as fortified food from the diets of young women who had been electively exposed to chronic fortification. OBJECTIVE: The objective was to examine the effect on folate status of foods fortified with low amounts of folic acid. DESIGN: We investigated the changes in dietary intakes and in red blood cell and serum concentrations of folate in response to removing folic acid-fortified foods for 12 wk from the diets of women who reportedly consumed such foods at least once weekly (consumers). RESULTS: Consumers (n = 21) had higher total folate intakes (P = 0.002) and red blood cell folate concentrations (P = 0.023) than nonconsumers (women who consumed folic acid-fortified foods less than once weekly; n = 30). Of greater interest, a 12-wk intervention involving the exclusion of these foods resulted in a decrease in folate intake of 78 +/- 56 microgram/d (P < 0.001), which was reflected in a significant reduction in red blood cell folate concentrations (P < 0.05). CONCLUSIONS: Cessation of eating folic acid-fortified foods resulted in removing 78 microgram folic acid/d from the diet. Over 12 wk this resulted in a lowering of red blood cell folate concentrations by 111 nmol/L (49 microgram/L). This magnitude of change in folate status in women can be anticipated as a result of the new US fortification legislation and is predicted to have a significant, although not optimal, effect in preventing neural tube defects.     

Folate Status of Young Canadian Women after Folic Acid Fortification of Grain Products

Women of childbearing age are advised to consume folic acid–containing supplements. Whether this remains necessary after folic acid fortification of the food supply in North America has yet to be determined. The objectives of this study were to assess folate intakes and the contribution of folic acid to the diets of women of childbearing age in the post–folic acid fortification era. Using a cross-sectional study design, fasting blood samples were obtained from 95 women (aged 18 to 25 years), and the samples were analyzed for serum and red blood cell folate, as well for total homocysteine. Dietary and supplemental folate intakes were assessed. The biochemical evidence showed that no women were folate deficient, but only 14% reached red blood cell folate concentrations associated with significant reductions in neural tube defect risk. Mean dietary intake of food folic acid was 96±64 μg/day, supplemental folic acid was 94±189 μg/day, natural folate was 314±134 μg/day, and the total intake, as dietary folate equivalents, was 646±368 μg dietary folate equivalents/day. Therefore, intakes of folic acid from fortified foods are within the level originally predicted for the fortification efforts; however, only 17% of participants met the special recommendation for women capable of becoming pregnant (400 μg folic acid daily from supplements, fortified foods, or both in addition to consuming food folate from a varied diet). These data suggest that women of childbearing age are achieving positive folate status in the postfortification era, but it may not be sufficient to achieve red blood cell folate concentrations associated with a significant reduction in neural tube defect risk. Even with food fortification, women of childbearing age should be advised to take a folic acid–containing supplement on a daily basis.     

A comparison of the effect of advice to eat either '5-a-day' fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine

OBJECTIVE: To assess and compare the effects of natural folate (100 micro g) with those of folic acid from fortified sources (100 micro g/day) on plasma folate and homocysteine. DESIGN: Randomized controlled trial (parallel groups). SETTING: Men and women living in South Wales, UK. SUBJECTS: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). INTERVENTIONS: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet-usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet-usual diet plus 100 microg/day folate from natural sources; (3) control-usual diet. RESULTS: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P<0.001) achieving an extra 98 microg/day (95% CI 88-108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P<0.001), but achieved a mean increase of only 50 microg/day (95% CI 34-66). Plasma folate increased (P<0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8-5.1; natural group 2.76, 95% CI 0.6-4.9. Plasma homocysteine, vitamins B(6) and B(12) were not significantly changed. CONCLUSIONS: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes.     

Human folate bioavailability

The vitamin folate is recognized as beneficial health-wise in the prevention of neural tube defects, anemia, cardiovascular diseases, poor cognitive performance, and some forms of cancer. However, suboptimal dietary folate intake has been reported in a number of countries. Several national health authorities have therefore introduced mandatory food fortification with synthetic folic acid, which is considered a convenient fortificant, being cost-efficient in production, more stable than natural food folate, and superior in terms of bioavailability and bioefficacy. Other countries have decided against fortification due to the ambiguous role of synthetic folic acid regarding promotion of subclinical cancers and other adverse health effects. This paper reviews recent studies on folate bioavailability after intervention with folate from food. Our conclusions were that limited folate bioavailability data are available for vegetables, fruits, cereal products, and fortified foods, and that it is difficult to evaluate the bioavailability of food folate or whether intervention with food folate improves folate status. We recommend revising the classical approach of using folic acid as a reference dose for estimating the plasma kinetics and relative bioavailability of food folate.     

Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women

OBJECTIVE: We investigated the effects of mineral water fortified with folic acid, vitamins B(6), B(12), D and calcium on folate concentrations in serum and erythrocytes, serum vitamin B(12) and plasma homocysteine concentrations in free-living subjects. In addition, we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity. DESIGN: Randomized, controlled, double-blinded, parallel design. SETTING: Outpatient dietary intervention with free-living subjects in Eastern Finland. SUBJECTS: Altogether, 66 subjects were recruited for the study. In all, 60 subjects completed the study. INTERVENTIONS: The study began with a 2-week run-in period followed by an 8-week intervention period. During the intervention study, subjects consumed mineral water fortified with folic acid (563 microg/day), vitamins B(6) (1 mg/day), B(12) (7.5 microg/day), cholecalciferol (0.6 microg/day) and calcium (563 mg/day) or placebo mineral water. RESULTS: The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1+/-5.6 nmol/l (P<0.001) and 199+/-76 nmol/l (P<0.001), respectively, and decreased plasma homocysteine concentration by 1.6 micromol/l (P<0.001). Urinary calcium excretion and serum alkaline phosphatase activity for 24 h increased significantly (P<0.001 and P=0.01 respectively) in the intervention group. CONCLUSIONS: Mineral water fortified with folic acid, vitamins B(6), B(12) and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency. Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable.     

The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States

OBJECTIVE: Since January 1998, the Federal Drug Administration has required folic acid fortification of all enriched cereal-grain products in the U.S. This program intended to increase folic acid intake among women of childbearing age in order to decrease their risk of pregnancies affected by neural tube defects. The aim of this study was to explore the changes in serum and erythrocyte folate status of the adult U.S. population following folic acid fortification of enriched cereal-grain products and to explore accompanying changes in food sources and dietary total folate intake. METHODS: We compared data from two National Health and Nutrition Examination Surveys (NHANES): NHANES III, conducted during 1988 to 1994, reflecting the time prior to folate fortification, and NHANES 1999-2000, reflecting the time period after fortification. RESULTS: Mandatory folic acid fortification led to significant increases in both serum and erythrocyte folate concentrations in all sex and age groups. In the overall study population the mean serum folate concentration increased more than two-fold (136%), from 11.4 nmol/L to 26.9 nmol/L, and the mean erythrocyte folate concentration increased by 57 percent, from 375 nmol/L to 590 nmol/L. Less than 10% of women of childbearing age reached the recommended erythrocyte folate concentration of greater than 906 nmol/L that has been shown to be associated with a significant reduction in neural tube defect (NTD) risk. After fortification, the category "bread, rolls, and crackers" became the single largest contributor of total folate to the American diet, contributing 15.6% of total intake, surpassing vegetables, which were the number one folate food source prior to fortification. Dietary intake of total folate increased significantly in almost all sex and age groups, except in females over 60 years of age. The mean dietary total folate intake of the study population increased by 76 microg/d (28%), from 275 microg/d to 351 microg/d. CONCLUSIONS: The fortification of enriched cereal-grain products with folic acid led to a significant improvement of blood folate status of the overall adult, non-supplement using, US population. However, women of childbearing age may take folic acid supplements to reach erythrocyte folate levels that have been associated with decreased risk of NTDs.     

Fortifying food with folic acid improves folate intake in German infants, children, and adolescents

Folate is a critical nutrient and programs to enhance folate intake have been established or are under consideration. We investigated to what extent consumers (C) profit from folic acid-fortified food and dietary supplements compared to nonconsumers (NC) of these products. A total of 6135 weighed records from 861 subjects (47% males, 53% females, age 6 mo to 18 y) from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study between 1990 and 2001 were evaluated. In 61% of the records, at least 1 item fortified with folic acid was reported, and in total 644 different items with a wide range of fortification levels were found. These were primarily commercial infant food (i.e., infant formula, weaning food) (44%), breakfast cereals (20%), and soft drinks (11%). Median dietary folate equivalents (DFEs) in NC increased from 65 and 62 microg/d in boys and girls at 6-12 mo of age, respectively, to 184 and 143 microg/d in adolescents 15-18 y of age. In C, DFEs increased from 109 and 100 microg/d in boys and girls at 6-12 mo of age, respectively, to 370 and 276 microg/d in adolescents 15-18 y of age. Irrespective of gender, NC had 50-70% the DFE intakes of C with a tendency for higher percentages in younger than in older children and adolescents. Folate intakes by male and female consumers of fortified food or supplements exceeded the upper levels in 1.7 and 1.2% of subjects, respectively. Currently, a fortification program for staple foods (e.g., grain products) does not seem necessary in Germany if children and adolescents consume food already fortified with folic acid.     

Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001-2002

BACKGROUND: Neural tube defects are serious birth defects of the brain and spinal cord. Up to 70% of neural tube defects can be prevented by the consumption of folic acid by women before and early during pregnancy. OBJECTIVE: The objective was to examine folic acid intake in women of childbearing age in the United States. DESIGN: We analyzed nutrient intake data reported by 1685 nonpregnant women aged 15-49 y who participated in the National Health and Nutritional Examination Survey, 2001-2002. RESULTS: The adjusted geometric mean consumption of folic acid from fortified foods was 128 microg/d (95% CI: 123, 134 microg/d) in nonpregnant women. Eight percent (95% CI: 5.8%, 11.0%) of nonpregnant women reported consuming >or=400 microg folic acid/d from fortified foods. This proportion was lower among non-Hispanic black women (5.0%) than among non-Hispanic white (8.9%) or Hispanic (6.8%) women. A smaller percentage of non-Hispanic black (19.1%) and Hispanic (21%) women than of non-Hispanic white women (40.5%) consumed >or=400 microg folic acid from supplements, fortified foods, or both, in addition to food folate, as recommended by the Institute of Medicine to reduce the frequency of neural tube defects. CONCLUSIONS: Most nonpregnant women of childbearing age in the United States reported consuming less than the recommended amount of folic acid. The proportion with low daily folic acid intake was significantly higher in non-Hispanic black and Hispanic women than in non-Hispanic white women. At the present level of folic acid fortification, most women need to take a folic acid-containing dietary supplement to achieve the Institute of Medicine recommendation.     

An update on folates and folic acid: contribution of MAFF‐funded research

The Ministry of Agriculture, Fisheries and Food (MAFF) recently commissioned the British Nutrition Foundation to review critically its Optimal Nutrition Status programme and identify future research requirements. MAFF describes two main scientific objectives for this programme: (a) to understand the links between optimal nutrition status and the maintenance of good health, and (b) to develop accurate measures of bioavailability of micronutrients from foods. Five projects funded under this programme have been concerned with folates and folic acid. The B vitamin folate/folic acid occurs in food as folic acid (the synthetic form used for fortification and dietary supplements) and a range of naturally occurring folate vitamers (folates). Measurement of folates in foods and biological samples has been difficult because of the different natural forms of folate. Several MAFF‐funded projects have addressed this difficulty and new assays for food folates and folates in biological samples have been developed. There is good evidence that the synthetic form of the vitamin, folic acid, in its free form as in supplements, is stable and more bioavailable than the naturally occurring folates at typical intake levels, but its bioavailability from fortified foods is less well established. Understanding of the bioavailability of endogenous food folates is also incomplete, and it is not possible at this time to predict the bioavailability for a given diet. Stable isotopic methods, as used in some of the MAFF‐funded projects, show great promise for the determination of folate bioavailability in whole diets, fortified foods and dietary supplements. An understanding of the function and metabolism of folates/folic acid is critical in identifying indicators of status. Recent and current research (some funded by MAFF), especially that relating to plasma homocysteine as a functional marker, is described in this paper. Human intervention studies that are being used to determine dose response of both natural food folates, and folic acid in fortified foods and supplements are also described. As yet there is insufficient evidence to determine functional markers of optimal nutrition status of folates/folic acid in population groups and hence to be in a position to review the Dietary Reference Values. Further research requirements were identified in the review and refined at a workshop of experts. These are set out under individual MAFF programme objectives in a table at the end of the paper.     

Folate promotion in Western Australia and the prevention of neural tube defects

OBJECTIVES: We conducted a case-control study to investigate the effectiveness of efforts to increase folate intake in Western Australia (WA) for the prevention of neural tube defects (NTD). METHODS: Case (36) and control (578) mothers completed questionnaires, from which their intake of folate from supplements and food (including fortified foods) was estimated. RESULTS: Almost one-third of women took folic acid supplements periconceptionally. Supplement use was associated with a non-significant 4% reduction in risk. For women not taking supplements, dietary sources of folate were protective, and most women obtained at least some folate from fortified food. CONCLUSIONS: For the two-thirds of WA women not taking supplements, fortified food is an important source of folate for the prevention of NTD. IMPLICATIONS: Greater promotion of foods currently allowed to be fortified with folate, or mandatory fortification, is needed to maximise prevention of NTD in Australia.     

Folate: a key to optimizing health and reducing disease risk in the elderly

Inadequate folate status is associated with an increased risk for chronic diseases that may have a negative impact on the health of the aging population. Folate, a water-soluble vitamin, includes naturally occurring food folate and synthetic folic acid in supplements and fortified foods. Inadequate folate status may result in hyperhomocysteinemia, a significant risk factor for atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects and increased risk for cognitive dysfunction. Folate status may be negatively influenced by inadequate intake, genetic polymorphisms and interactions with various drugs. In the US, folic acid is now added to enriched grain products and continues to be included in the majority of ready-to-eat breakfast cereals. Recent data indicate that the folate status in the US population has improved significantly, presumably due to the effects of fortification. Folic acid (not food folate) intake in excess of the Tolerable Upper Intake Level may mask the diagnosis of a vitamin B(12) deficiency, which is more prevalent in the elderly than younger individuals. When folic acid supplements are recommended, a multivitamin that includes vitamin B(12) should also be advised. To safely and effectively increase folate intake in the elderly, naturally occurring folate-rich food sources should be promoted. Folate-rich foods include orange juice, dark green leafy vegetables, asparagus, strawberries and legumes. These foods are also excellent sources of other health-promoting nutrients associated with chronic disease risk reduction.     

The impact of voluntary fortification of foods on micronutrient intakes in Irish adults

The objective of this work was to quantify the impact of the voluntary fortification of foods on dietary intakes of vitamins and minerals of Irish adults. Foods that were voluntarily fortified were identified and pre- and post-fortification levels of micronutrients were determined from data supplied by manufacturers and food composition tables. Using food consumption data in 1379 adults aged 18-64 years, estimated using a 7-d food diary during the North/South Ireland Food Consumption Survey, intakes of micronutrients were determined, both including and excluding the fortification component in foods. Of approximately 3000 foods recorded as consumed, 1.9 % were fortified, mainly breakfast cereals and beverages. Median micronutrient content of fortified foods (FF) ranged from 18-33 % EC RDA per typical serving. Among consumers (65 % of men, 68 % of women), FF contributed, on average, 3.9 % (men) and 5.0 % (women) to mean daily intake (MDI) of energy. Relative to their contribution to MDI of energy, FF contribute a greater % MDI for Fe (men 16, women 19), folate (men 18, women 21), vitamins B1 (men 14, women 16), B2 (men 16, women 18), B6 (men 12, women 15), D (men 5, women 11), B12 (men 5, women 7) and niacin (men 10, women 12). Fortification significantly improved the adequacy of intake of some micronutrients, particularly of riboflavin, folate, vitamin D and Fe in women and did not contribute to an increased risk of adverse effects from excessive intake of any micronutrient.     

Dietary intake of folate by adolescents and the potential effect of flour fortification with folic acid

The UK Department of Health recently recommended that flour be fortified with folic acid, at 2400 microg/kg. The objectives of the present paper were: to determine the consequence of this on folic acid intake of adolescents; to determine the level of fortification necessary to achieve an intake of 400 microg/d in adolescent girls (the amount recommended periconceptionally); to estimate the consequence of fortification on folic acid intake of high flour consumers; and to report on folate intake of adolescents. Dietary intake of folate and flour were determined by analysis of an existing database of the diets of 379 English adolescents. The folic acid intake that would result from white flour fortification with folic acid at 2400 microg/kg was determined and the level of folic acid fortification necessary to achieve an intake of 400 microg/d in girls from this source was also calculated. Without flour fortification, 6.9 % of girls failed to reach the UK lower reference nutrient intake for total folate. Fortification of white flour with folic acid at 2400 microg/kg would result in an additional folic acid intake of 191(sem 6) microg/d in girls. To ensure 97 % of girls received 400 microg/d from white flour, white flour would need to be fortified at a level of 10 430 microg/kg, resulting in intakes of 1260 microg/d from flour in the highest (97.5 centile) female white flour consumers and 1422 microg/d from flour in the highest (97.5 centile) male white flour consumers.     

Effect of food fortification on folic acid intake in the United States

BACKGROUND: The addition of folic acid to all enriched cereal-grain foods, mandated by the Food and Drug Administration (FDA), was initiated in January 1998. Although this program was designed such that typical folate intakes would be increased by approximately 100 micro g/d and that the risk of intakes > 1000 micro g/d (the FDA's safe upper limit of daily intake) would be minimal, its actual effect on folate intake has yet to be determined. OBJECTIVE: The objective was to estimate the effect of folic acid fortification on the amount of folate consumed by persons in the United States. DESIGN: Linear regression analysis of data from published studies was used to determine the relation between a chronic folic acid dose and the resulting increase in steady state concentrations of folate in plasma or serum. Using this regression equation and reverse prediction, we quantified the increase in folic acid intake from fortification required to achieve the increase in plasma or serum folate observed in published studies. RESULTS: The increase in circulating folate concentration was linearly related to folic acid intake over the range of 100-1000 micro g/d (r = 0.984, P < 0.0001). Predicted increases in folic acid intake from fortified food ranged from 215 to 240 micro g/d. CONCLUSIONS: Typical intakes of folic acid from fortified foods are more than twice the level originally predicted. The effect of this much higher level of fortification must be carefully assessed, especially before calls for higher levels of fortification are considered.     

Short-term folate,vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages

Based on research demonstrating associations between folate, B-12 and B-6 vitamins and cognition and mood, we investigated the effects of short-term supplementation in 211 healthy younger, middle-aged and older women who took either 750 microg of folate, 15 microg of vitamin B-12, 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition, we examined associations between dietary intake of these vitamins and cognition and mood. Usual dietary intake status was estimated using a retrospective, self-report, quantified food frequency questionnaire. Participants completed alternate forms of standardized tests of cognitive processing resources, memory, executive function, verbal ability and self-report mood measures before and after supplementation. Supplementation had a significant positive effect on some measures of memory performance only, and no effect on mood. Dietary intake status was associated with speed of processing, recall and recognition and verbal ability.     

Folic acid intake from fortification in United States exceeds predictions

In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 micro g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was approximately 1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 micro g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected.     

Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods

Objective: To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid.

Methods: Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis.

Results: Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0–52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency (<7 nmol/L) in 10 (6.9%) participants. No one had vitamin B12 deficiency (<148 pmol/L). An elevated serum UMFA concentration was defined as > 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] = 1.02 [1.01–1.04)] and being a male (OR [95% CI] = 0.40 [0.19–0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively.

Conclusion: UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.