Plasma, liver and kidney folate and plasma homocysteine concentrations are poor response variables at very low dietary folate intakes, in a folate depletion/repletion rat model

Folate depletion/repletion rat models are popular protocols for assessing the bioavailability of folate. Much of the early work carried out on folate bioavailability concentrated on foods naturally high in folate. However, foods low in folate often contribute significantly to folate intake because of their high consumption in the general population. Therefore, the assessment of the bioavailability of foods low in folate is essential to properly estimate folate intake. The present study investigated plasma, liver and kidney folate and plasma homocysteine concentrations as appropriate response variables for measuring folate bioavailability in the rat at very low dietary folate intakes. One hundred and one weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1% succinyl sulfathiazole for 28 d. Following depletion, six rats were randomly assigned to each of 16 repletion diets containing folic acid, fortified white bread, unfortified wholemeal bread or unfortified rye bread calculated to provide 6.25, 12.5, 18.75 and 25 micrograms folate/kg of each diet. After a further 28 d, plasma, liver and kidney folate concentrations were determined by microbiological assay. Plasma homocysteine was measured by HPLC as a functional indicator of folate status. Only a weak correlation was found between the response variables measured and dietary folate intake, indicating that this folate depletion/repletion rat model is not suitable for testing the response of rats fed diets containing very low levels of folate.     

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.     

Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults

BACKGROUND: Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis. OBJECTIVE: The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population. DESIGN: The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18-92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake. RESULTS: Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179-197 microg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 micromol/L lower in the group with the highest fortified food intake (median intake: 208 microg/d folic acid) than in the nonconsumers of fortified foods (0 microg/d folic acid). CONCLUSIONS: These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.     

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.     

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.     

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).     

Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification

BACKGROUND: A relation between low folate status and depression has been recognized since the 1960s. Since 1998, flour in the United States has been fortified with folic acid, and the prevalence of folate deficiency has decreased dramatically. OBJECTIVE: We investigated whether, in this era of folic acid fortification, low folate status is a determinant of depressive symptoms in a cohort of elderly Latinos (aged >/=60 y) participating in the Sacramento Area Latino Study on Aging (SALSA). DESIGN: In a cross-sectional logistic regression analysis of data from SALSA (n = 627 M, 883 F), odds ratios (ORs) were ascertained for elevated depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D) score >/=16] among tertiles of plasma folate. Depressive symptoms were assessed by using the CES-D. Plasma folate concentrations were determined by radioassay. RESULTS: The prevalence of folate deficiency (plasma folate 相似文献   

Tissue distribution and prediction of total body folate of rats

To clarify relationships between dietary folic acid intake, blood levels and body stores of folate, rats were fed an amino acid-based diet supplemented with 0, 0.125, 0.5, 1, 2 or 4 mg folic acid/kg diet for 25 d. Folate concentrations of carcass, liver, gastrointestinal (GI) tract, kidney, spleen, testes, heart and lung from rats fed the folate-free diet were 0.06 +/- 0.01, 0.73 +/- 0.08, 0.05 +/- 0.01, 0.39 +/- 0.01, 0.05 +/- 0.01, 0.17 +/- 0.01, 0.02 +/- 0.01 and 0.02 +/- 0.01 micrograms/g, respectively. Serum and erythrocyte concentrations and total body stores were 0.88 +/- 0.16 ng/mL, 0.30 +/- 0.01 micrograms/mL and 13.9 +/- 0.7 micrograms, respectively. Body folate distribution was carcass, 55.6 +/- 1.4%; liver, 26.0 +/- 1.9%; erythrocytes, 7.7 +/- 0.4%; kidney, 4.8 +/- 0.2%; GI tract, 3.0 +/- 0.2%; and testes, 2.5 +/- 0.2%. Carcass content dropped to 38% whereas liver content increased to 44% in rats fed the highest dietary level. Tissue concentrations were correlated with one another and with dietary folate levels. Under these experimental conditions total body folate could be predicted from serum folate, but the general applicability of this relationship requires further study.     

Rat bioassay of wheat bran folate and effects of intestinal bacteria

This study estimates the folate endogenous to a food material (wheat bran) and examines the role of intestinal bacteria in the rat bioassay for folate. After a 4-wk folate depletion period, rats were fed for an additional 4 wk basal diets with or without 0.5% phthalylsulfacetamide and with 100, 200 or 300 g of wheat bran; or 50, 100 or 150 g of xylan; or 0, 0.25, 0.50 or 0.75 mg of folic acid added per kg of basal diet. Xylan increased both liver and fecal folate, and this effect was nearly eliminated by phthalylsulfacetamide. Wheat bran contributed 1.6 micrograms of available folate per g of wheat bran without phthalylsulfacetamide in an apparently valid slope-ratio analysis. With the addition of phthalylsulfacetamide, liver folate increased in rats fed wheat bran diets and decreased in rats fed folic acid diets. The slope-ratio analysis for wheat bran folate with phthalylsulfacetamide became invalid due to a lack of intersection. Phthalylsulfacetamide had no effect on fecal folate excretion from rats fed the wheat bran diets. Further studies are needed on a variety of foods with and without phthalylsulfacetamide to evaluate the effect and importance of intestinal folate synthesis in the rat.     

Will mandatory folic acid fortification prevent or promote cancer?

An overwhelming body of evidence for a protective effect of periconceptional folic acid supplementation against neural tube defects (NTDs) led to mandatory folic acid fortification in the United States. The effectiveness of folic acid fortification in improving folate status has already been shown to be quite striking, with a dramatic increase in blood measurements of folate in the United States. Preliminary reports also suggest a significant reduction ( approximately 15-50%) in NTDs in the United States. The success of folic acid fortification in improving folate status and in reducing NTD rates is truly a public health triumph and provides a paradigm of collaboration between science and public health policy. Although folic acid is generally regarded as safe, there continues to be concern that folic acid fortification may have adverse effects in subpopulation groups not originally targeted for fortification. In this regard, an emerging body of evidence suggests that folic acid supplementation may enhance the development and progression of already existing, undiagnosed premalignant and malignant lesions. Over the past few years, the US population has been exposed to a significant increase in folate intake, for which essentially no data on safety exist. The potential cancer-promoting effect of folic acid supplementation needs to be considered in carefully monitoring the long-term effect of folic acid fortification on the vast majority of the US population, who are not at risk of NTDs.     

High folate levels in Aboriginal children after subsidised fruit and vegetables and mandatory folic acid fortification

Objective : To evaluate the impact of a fruit and vegetable (F&V) subsidy program for disadvantaged Aboriginal children in Australia, implemented alongside the introduction of mandatory folic acid fortification of bread‐making flour. Methods : A before‐and‐after evaluation was undertaken of a F&V subsidy program at three Aboriginal community‐controlled health services in New South Wales. The program provided a weekly box of subsidised F&V linked to preventive health services and nutrition promotion for families. In this analysis, red blood cell (RBC) folate was assessed together with self‐reported dietary intake at baseline and 12 months later in a cohort of 125 children (aged 0–17 years). Results : No children had low RBC folate at baseline or at follow‐up; however, 33 children (26%) exceeded the reference range of RBC folate at baseline and 38 children (30%) exceeded the reference range at follow‐up. Mean RBC folate levels increased substantially in children at follow‐up (mean RBC folate z‐score increased +0.55 (95%CI 0.36–0.74). Change in F&V intake (p=0.196) and mean bread intake (p=0.676) were not statistically significant predictors for change in RBC folate levels. Conclusions : RBC folate levels increased among these disadvantaged Aboriginal children following mandatory folic acid fortification and participation in a subsidised F&V program. Even before mandatory folic acid fortification, none of these children had low RBC folate. Implications : The effect on health of mandatory fortification of foods with folate is not clear, hence, ongoing population‐based monitoring of folate levels to assess the impact of mandatory folic acid fortification is important.     

Research goals for folate and related B vitamin in Europe

In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, for example, among women of child-bearing age who could lower the risk of having a baby with a neural tube defect, food-based strategies aimed at increasing the intake of folate and other B-group vitamins should be a priority for future research. These should include the development of a combined strategy of supplemental folate (possibly with vitamin B(12)), biofortification using engineered plant-derived foods and micro-organisms and food fortification for increasing folate intakes in the general population. Currently, the most effective population-based strategy to reduce NTDs remains folic acid fortification. However, the possible adverse effect of high intakes of folic acid on neurologic functioning among elderly persons with vitamin B(12) deficiency needs urgent investigation. The results of ongoing randomized controlled studies aimed at reducing the prevalence of hyperhomocysteinemia and related morbidity must be available before food-based total population approaches for treatment of hyperhomocysteinemia can be recommended. Further research is required on quantitative assessment of folate intake and bioavailability, along with a more thorough understanding of physiological, biochemical and genetic processes involved in folate absorption and metabolism.     

A survey of folate knowledge and consumer behaviours in Western Australia prior to the introduction of mandatory food fortification

Objectives: Prior to the introduction of mandatory folic acid fortification in September 2009, this study collected baseline data on folate awareness, knowledge of pregnancy‐relevant public health messages and consumer behaviours in Western Australia. Methods: One thousand residents aged 18 years or older participated in a cross sectional telephone survey in September 2006. Respondents were recruited randomly from the electronic residential telephone directory. Results: Most respondents reported knowing little or nothing about folate (86%). Women of childbearing age were more likely than other adults to know the association between folate intake and birth defects (82% v 56%) but 41% did not know that folate should be consumed periconceptionally to reduce the risk of spina bifida. Overall, half the respondents did not take supplements and two‐thirds did not know if the food products they ate were fortified with folic acid. Associations were detected between knowledge, consumer behaviours and socio‐economic indicators such as age, income, highest level of education, area of residence and parental status. Implications: A mix of public health strategies that includes mandatory fortification and the promotion of supplement use should improve the timely and sufficient intake of folate across all socio‐economic strata of the Australian population. Strategies that support the introduction of mandatory fortification, such as awareness and education campaigns should be built on a solid understanding of the drivers and barriers to knowledge acquisition and desired consumer behaviours.     

Effect of folic acid fortification of foods on folate intake in female smokers with cervical dysplasia

OBJECTIVE: We investigated the effect of folic acid fortification of enriched cereal grains on folate intake in women of predominantly childbearing age at high risk for cervical cancer. METHODS: Subjects in this cross-sectional study were 77 women randomized between November 1999 and December 2000 in the Women's Intervention to Stay Healthy (WISH), a clinical trial evaluating the effect of a tobacco control intervention on the progression of cervical dysplasia. All subjects were cigarette smokers, had a previously abnormal Papanicolaou test, and were positive for high-risk human papillomavirus at entry. Dietary intake was assessed with food-frequency questionnaires completed at the baseline visit for WISH. The effect of folic acid fortification on folate intake was assessed by using pre- and postfortification folate databases to estimate folate intake. RESULTS: Mean folate intake assessed with the postfortification database was 63% higher than intake assessed with the prefortification database: 417 versus 256 microg/d of dietary folate equivalents (P < 0.0001). The proportion of subjects below the estimated average requirement for folate was smaller after fortification than before fortification: 40.3% versus 75.3% (P < 0.0001). Several foods, including white bread, cheese dishes, spaghetti, and rice, became major sources of folate as a result of fortification. CONCLUSIONS: Folic acid fortification resulted in an increased intake of folate in these subjects. However, even with fortification, folate intake in a large proportion of these women remained below recommended levels. These results should be considered before decisions regarding future levels of folic acid fortification are made.     

Folic acid conjugase from plasma. III. Use of the enzyme in the estimation of folate activity in foods.

A convenient method for the estimation of food folates using human plasma as a source of folic acid conjugase has been standardized. Bovine, goat and dog plasma could not be used for the purpose because of low enzyme activity and slow reaction rates. Human plasma conjugase released food folates from conjugated forms over a pH range of 4.5 to 6.0. The food folate values obtained by employing rat liver and chicken pancreas conjugase closely agreed with the values obtained by using human plasma conjugase. The advantages in using human plasma as a source of conjugase were (1) easy availability (2) non-essentiality of preliminary processing (3) stability of the enzyme on storing plasma in cold (4) low enzyme blank folate activity and (5) low amount of plasma needed for assay. Using this method, folic acid activity of some common Indian foods of plant and animal origin has been estimated. There were wide variations in the folate activity of different classes of foods. In general legumes and green leafy vegetables were found to be rich in folate activity.     

Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.

Elevated total plasma homocysteine (tHcy) concentrations are considered a risk factor for neural tube defects (NTD) and cardiovascular disease. Supplementation with folic acid decreases the risk of women having children with NTD. In both sexes, it decreases tHcy levels. We investigated the efficacy of natural dietary folate in improving folate and homocysteine status. We performed a 4-wk dietary controlled, parallel design intervention trial with 66 healthy subjects (18-45 y) divided into 3 treatment groups: the dietary folate group, the folic acid group and the placebo group. Each day each group was fed a different diet. The dietary folate group received a diet high in vegetables and citrus fruit (total folate content approximately 560 microgram) plus a placebo tablet. The folic acid group received a diet naturally low in folate (approximately 210 microgram) plus 500 microgram folic acid and placebo tablet on alternate days, i.e., 250 microgram folic acid/d. And the placebo group received the same low-folate diet as the folic acid group plus a placebo tablet. After 4 wk of intervention, folate status improved, and tHcy concentrations decreased in both the dietary folate and the folic acid groups. From the amount of additional folate (350 microgram/d) and folic acid (250 microgram/d) consumed, the relative bioavailability of dietary folate compared to folic acid was calculated to be 60-98%, depending on the endpoint used. In conclusion, increasing the consumption of vegetables and citrus fruit, both good sources of folate, will improve folate status and decrease tHcy concentrations. This may contribute to the prevention of cardiovascular disease and NTD in the general population     

Supranormal dietary folic acid supplementation: effects on methionine metabolism in weanling rats

There are nationwide folic acid (FA) fortification programmes of staple foods established or under consideration in order to prevent neural tube defects. Universal FA fortification still remains controversial because of the concern that additional FA in the diets of population groups (e.g. children and elderly) not initially targeted for fortification may suffer adverse effects. However, dietary surveys regarding folate generally deal with adults and little is known about the consumption and long-term effects of fortified food and supplements in growing individuals. Recent reports from our laboratory show several effects of high-dose folate supplementation in rats. In the present work, we studied the effect of FA on the methionine cycle in weanling (3-week-old) male rats after 4 weeks of supplementation with 40 mg FA/kg diet v. control (1 mg FA/kg diet). FA supplementation resulted in a reduction of homocysteine and creatinine concentrations v. control group. FA supplementation did not alter S-adenosylmethionine/S-adenosylhomocysteine ratio, DNA methylation, enzymatic activities or concentrations of vitamins involved in the nutritional regulation of the methionine cycle, except for folate. FA supplementation of 40 mg/kg did not lead to hepatic or renal damage. In conclusion, there were no apparent adverse effects on one-carbon metabolism after FA supplementation in the studied conditions.     

Folic acid fortification increases red blood cell folate concentrations in the Framingham study.

In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs. 354 individuals who were examined after implementation of fortification (exposed). We calculated the prevalence of deficient (<160 microg/L, 362.6 nmol/L) and acceptable (>200 microg/L, 453.2 nmol/L) RBC folate concentrations in both groups. Those exposed to folic acid fortification had a mean RBC folate of 450.0 microg/L (1019.7 nmol/L), a value 38% higher than the mean RBC folate of 325.3 microg/L (737.1 nmol/L) in those who were not exposed to fortification (P < 0.001). The prevalence of individuals with deficient RBC folate was 4.9% in the group not exposed to fortification compared with 1.9% in the group exposed to fortification (P < 0.02), and the prevalence of individuals with acceptable RBC folate was 87.0% in the group not exposed to fortification compared with 96.1% in the group exposed to fortification (P < 0.001). Similar results were seen in individuals who used supplements containing B-vitamins. The results of this study showed that in this cohort, the introduction of folic acid fortification significantly improved folate nutritional status measured as RBC folate.     

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.     

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 μg/d (28%), from 275 μg/d to 351 μg/d.

Conclusions: The fortification of enriched cereal-grain products with folic acid lead 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.