Veronica Öhrvik

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.

Orange juice is a good folate source in respect to folate content and stability during storage and simulated digestion

BackgroundEstimated average folate intake in Sweden is less than 55% of the recommended daily intake (RDI) for women of childbearing age (Becker and Pearson in Riksmaten 1997–1998 Kostvanor och näringsintag i Sverige. National Food Administration, Uppsala, pp 34, 44, 121, 2002). Because a good folate status reduces the risk of neural tube defects, mandatory folic acid fortification is discussed in some European countries. This however, could lead to exposure to unintentionally high amounts of folic acid for some population groups, therefore targeted folic acid fortification could be an alternative.AimsTo (1) determine natural folate content in three popular brands of orange juice sold in Sweden, (2) determine stability of natural folate and folic acid fortificant during shelf life in a folic acid/iron fortified orange juice, (3) determine folate stability in four juices during simulated household consumption for one week and (4) determine the in vitro bioaccessibility of natural folate in one brand of orange juice using the TNO gastroIntestinal Model (TIM).MethodsNatural folate content in juices was determined using RP-HPLC-FL. To determine folic acid content and confirm RP-HPLC-FL values LCMS was used. Stability during shelf life was determined in unopened bottles of a folic acid/iron fortified juice and for one week in four popular juices under household consumption conditions with reopening of bottles daily. For an in vitro folate bioaccessibility experiment in orange juice the TNO TIM Model was used.Results5-CH3-H4folate was the dominant natural folate form in the juices with contents ranging from 16–30 µg/100 g. Shelf life losses of folic acid fortificant were 1–4%. During one week simulated household consumption 5-CH3-H4folate content decreased by up to 7% (n.s). Bioaccessibility of natural folate in orange juice was almost 100%. Most folate was released for absorption in jejunum between 60–120 min after trial start.ConclusionOrange juice may be considered a good source of natural folate in respect to content and stability during storage and simulated digestion. Moreover, added folic acid fortificant in a folic acid/iron fortified orange juice was stable during shelf life.

Folate bioavailability from breads and a meal assessed with a human stable-isotope area under the curve and ileostomy model

BACKGROUND Recent data revealed differences in human absorption kinetics and metabolism between food folates and folic acid supplements and fortificant. OBJECTIVE The objective was to determine folate bioavailability after ingestion of breads or a breakfast meal fortified with either 5-CH(3)-H(4) folate or folic acid by using a stable-isotope area under the curve (AUC) and ileostomy model. DESIGN In a randomized crossover trial, healthy ileostomists (n = 8) ingested single doses of whole-meal bread that contained ap 450 nmol (200 micro g) of either (6S)-[(13)C(5)]5-CH(3)-H(4) folate or [(13)C(5)]folic acid or a breakfast meal that contained ap 450 nmol (200 micro g) [(13)C(5)]folic acid. We collected blood from the subjects during 12 h postdose for assessment of plasma kinetics. Nonabsorbed folate was assessed from labeled folate contents in stomal effluent 12 and 24 h postdose. RESULTS The median (range) plasma AUC(0 rarr 12) (AUC from 0 to 12 h after ingested dose) of 66 nmol sdot h/L (34-84 nmol sdot h/L) after ingestion of bread that contained (6S)-[(13)C(5)]5-CH(3)-H(4) folate was significantly greater (P lt 0.001) than that after ingestion of [(13)C(5)]folic acid in fortified bread [28 nmol sdot h/L (15-38 nmol sdot h/L)] and a fortified breakfast meal [26 nmol sdot h/L (15-60 nmol sdot h/L)]. Both labeled doses resulted in increases of plasma [(13)C(5)]5-CH(3)-H(4) folate. However, the kinetic variables C(max) (maximum plasma concentration) and T(max) [time (min) of maximum plasma concentration] varied after ingestion of the different folate forms. The stomal folate content was lt 10% of the ingested dose and did not vary significantly after ingestion of test foods that contained (6S)-[(13)C(5)]5-CH(3)-H(4) folate [median (range): 13 nmol (10-31 nmol)] or [(13)C(5)]folic acid [median (range): 25 nmol (8-42 nmol)] (P = 0.33). CONCLUSIONS Our data confirm differences in plasma absorption kinetics for reduced folates and synthetic folic acid administered with the test foods. Stomal folate contents indicated almost complete bioavailability of labeled folate from the breads or breakfast meal.

Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty acids

Trans-fatty acids (TFA) have been associated with increased risk of coronary heart disease, by affecting blood lipids and inflammation factors. Current nutrition recommendations emphasise a limitation of dietary TFA intake. The aim of this study was to investigate fatty acid composition in sweet bakery products, with emphasis on TFA, on the Swedish market and compare fatty acid composition over time. Products were sampled in 2001, 2006 and 2007 and analysed for fatty acid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001 of total fatty acids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41 products had TFA levels above 2% of total fatty acids. TFA content had decreased in this product category, while the proportion of saturated (SFA) and polyunsaturated (PUFA) fatty acids had increased, mostly through increased levels of 16:0 and 18:2 n-6, respectively. The total fat content remained largely unchanged.

Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial

BACKGROUND Ten years after the introduction of mandatory folic acid fortification in the United States, Canada, and Costa Rica, the issue is still under debate in several countries, and Sweden recently decided against mandatory fortification. OBJECTIVE The objective was to determine the folate status of women after an intervention involving 2 Swedish dietary recommendations: a food recommendation (bread) and a complete meal recommendation (breakfast). DESIGN Fifty-one free-living women with normal folate status participated in a 12-wk controlled intervention trial. Subjects were randomly assigned to one of the following interventions: apple juice (control group; n = 17), a breakfast providing 125 microg folate (breakfast group; n = 17), or 5 slices of whole-meal bread to be eaten over the course of the day, which provided 70 microg folate (bread group; n = 17). Folate status was assessed on the basis of concentrations of erythrocyte folate, serum folate, and plasma total homocysteine (tHcy) at baseline and at weeks 8 and 12 of the trial. RESULTS In the breakfast group, initial median concentrations of erythrocyte folate (805 nmol/L) increased by 172 nmol/L (95% CI: 24, 293; P = 0.02) relative to the control. The relative increase in initial serum folate (2 nmol/L, 95% CI: 0, 5; P = 0.06) was nonsignificant. The initial tHcy concentration (8.7 micromol/L) decreased by 2.3 micromol/L (95% CI: -1, -3.4; P < 0.01). In the bread group, the initial tHcy concentration (9.1 micromol/L) decreased nonsignificantly by 1.4 micromol/L (95% CI: 0, -2.8; P = 0.08) relative to the control group, whereas other outcomes were stable. CONCLUSIONS The folate status of the subjects improved after regular consumption of the breakfast meal. The additional folate intake from the bread maintained the folate status but was not sufficient to improve it.

Dietary habits, nutrient intake and biomarkers for folate, vitamin D, iodine and iron status among women of childbearing age in Sweden

Abstract Background: Dietary intake and nutritional status are important for pregnancy and pregnancy outcomes. Dietary advice on folate, targeted to women of childbearing age, aims at preventing neural tube defects in the offspring. Aim: To describe food and nutrient intake and nutritional status among women of childbearing age in Sweden in relation to current nutrition recommendations. Methods: Dietary intake was assessed using a web-based four-day consecutive food record among adults aged 18–80 years—‘Riksmaten 2010–11 adults’. In a subsample, biomarkers of folate, vitamin D, iodine, and iron status were assessed. Results: Women of childbearing age had lower intakes of fruit and vegetables, fish, and whole grains, but higher intakes of soft drinks. Macronutrient composition was generally in line with the Nordic Nutrition Recommendations, except for a lower intake of fibre, a higher intake of saturated fatty acids, and added sugars. Mean intakes of vitamin D, folate, and iron were below recommended intakes (RI). Median urinary iodine concentration (UIC) was 74 μg/L, 20% had insufficient vitamin D status, and 3% low folate concentrations with no age differences. Furthermore, 29% of women 18–44 years of age had depleted iron stores. Conclusions: The dietary pattern among women of childbearing age (18–44 years) was less favourable compared to older women. Intakes of some micronutrients were below RI, but no differences in vitamin D, folate, or iodine status between age groups were observed. However, improvements of folate and iodine status among women of childbearing age are warranted. This can be achieved by following dietary guidelines including use of folic acid-containing supplements.

Quantification of Isotope-Labeled and Unlabeled Folates and Folate Catabolites in Urine Samples by Stable Isotope Dilution Assay

Dual-label stable isotope dilution assays for the simultaneous quantification of isotopologic folates in clinical samples offer the perspective for differentiating between unlabeled folates from endogenous body pools and administered [13C5]-labeled folates from a test dose when performing bioavailability trials. In contrast to intact folates, this methodology could hitherto not be applied to the quantification of the folate catabolites, p-aminobenzoyl glutamate and p-acetamidobenzoyl glutamate. In this study, [2H4]-p-aminobenzoyl glutamate, [2H4]-p-acetamidobenzoyl glutamate, and unlabeled p-acetamidobenzoyl glutamate were synthesized. The synthesis of the [2H4]-labeled compounds started at unlabeled p-aminobenzoic acid. For the formation of p-acetamidobenzoyl glutamate, p-aminobenzoyl glutamate was acetylated. The new substances were applied successfully in stable isotope dilution assays for the simultaneous quantification of the [13C5]-labeled and unlabeled folate catabolites, p-aminobenzoyl glutamate and p-acetamidobenzoyl glutamate, along with the predominant folate vitamers in urine. The assays were based on clean-up by strong anion exchange followed by liquid chromatography-tandem mass spectrometry detection. Assay sensitivity was sufficient to detect the folate catabolites in physiologic concentrations. The limit of detection was below 0.4 and 0.3 nmol/100 g for p-aminobenzoyl glutamate isotopologues and p-acetamidobenzoyl glutamate isotopologues in urine, respectively. The successful synthesis of [2H4]-p-aminobenzoyl glutamate, [2H4]-p-acetamidobenzoyl glutamate, and unlabeled p-acetamidobenzoyl glutamate and the implementation of these substances in stable isotope dilution assays allows dual-label designs that provide a more detailed insight into human folate metabolism.

Improving food composition data by standardizing calculation methods

Food composition data is important in nutritional policy making. However, food analyses are expensive and to use analysed values only is not economically justifiable; hence recipe calculations are ...