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  • 1. Arkbåge, Karin
    et al.
    Verwei, Miriam
    Havenaar, Robert
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate decreases after the addition of folate-binding protein to yogurt as studied in a dynamic in vitro gastrointestinal model.2003In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 133, no 11, p. 3678-3683Article in journal (Refereed)
    Abstract [en]

    Milk products are only moderate sources of folate. Nevertheless, they are of interest due to their content of folate-binding proteins (FBP), which in some studies have been reported to increase folate bioavailability. The effect of FBP on folate bioavailability has been widely discussed. The aim of this study was to investigate the bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate (5-CH3-H4folate) from fortified yogurt using a dynamic in vitro gastrointestinal model (TIM). In addition, the effect of FBP on folate bioaccessibility and the stability of FBP added to yogurt during gastrointestinal passage were investigated. Folate bioaccessibility was 82% from yogurt fortified with folic acid and 5-CH3-H4folate. The addition of FBP to yogurt decreased (P < 0.05) folate bioaccessibility. The lowering effect of FBP was more pronounced in yogurt fortified with folic acid (34% folate bioaccessibility) than from yogurt fortified with 5-CH3-H4folate (57% folate bioaccessibility). After gastrointestinal passage, 17% of the FBP in yogurt fortified with 5-CH3-H4folate and 34% of the FBP in yogurt fortified with folic acid were recovered. No difference in folate bioaccessibility was found between folate-fortified yogurt and folate-fortified pasteurized milk (P = 0.10), whereas the lowering effect of FBP was (P < 0.05) greater in yogurt compared with pasteurized milk. In conclusion, based on the high bioaccessibility of folic acid and 5-CH3-H4folate, yogurt without active FBP can be considered to be an appropriate food matrix for folate fortification.

  • 2.
    Arkbåge, Karin
    et al.
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Fonden, Rangne
    Arla Foods Innovation.
    Jägerstad, Margaretha
    Swedish University of Agricultural Sciences.
    Retention of vitamin B-12 during manufacture of six fermented dairy products using a validated radio protein-binding assay2003In: International Dairy Journal, ISSN 0958-6946, E-ISSN 1879-0143, Vol. 13, no 2-3, p. 101-109Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to study vitamin B-12 retention during manufacture of six fermented dairy products. Careful validation of a commercial radio protein-binding kit showed this assay to be suitable after optimisation of sample pre-treatment and control of the kit for possible matrix effects. In fermented milks, vitamin B-12 concentrations decreased by 40-60%, compared with the starting milk, during storage of the final product at 4degreesC for 14 days, most likely attributed to consumption by starter cultures. In cottage cheese, hard cheeses and blue cheese, 18-56% of the vitamin B-12 originally present in the milk was retained. Removal of the whey fraction was the dominant factor reducing vitamin B-12 retention in cheeses, while the fermentation by starter cultures hardly affected vitamin B-12 concentrations.

  • 3. Augustin, K
    et al.
    Frank, J
    Augustin, S
    Langguth, P
    Öhrvik, V
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Rimbach, G
    Wolffram, S
    Green tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study.2009In: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 60, no 3, p. 103-108Article in journal (Refereed)
    Abstract [en]

    Green tea catechins (GTC) have been shown to inhibit the activities of enzymes involved in folate uptake. Hence, regular green tea drinkers may be at risk of impaired folate status. The present experiments aimed at studying the impact of dietary GTC on folate concentrations and metabolism. In a human pilot study (parallel design) healthy men consumed for 3 weeks 6 capsules (approximately 670 mg GTC) per day (2 capsules with each principal meal) containing aqueous extracts of the leaves of Camellia sinensis (n=17) or placebo (n=16). No differences in plasma folate concentrations were observed between treatments. We further fed groups of 10 male rats diets fortified with 0, 0.05, 0.5, 1, or 5 g GTC/kg for 6 weeks. Only at the highest intake, GTC significantly decreased serum 5-methyl-tetrahydrofolate concentrations in rats, while mRNA concentrations of reduced folate carrier, proton-coupled folate transporter/heme carrier protein 1, and dihydrofolate reductase (DHFR) remained unchanged in intestinal mucosa. Using an in vitro enzyme activity assay, we observed a time- and dose-dependent inhibition of DHFR activity by epigallocatechin gallate and a green tea extract. Our data suggest that regular green tea consumption is unlikely to impair folate status in healthy males, despite the DHFR inhibitory activity of GTC.

  • 4.
    Bouckaert, Kimberley P
    et al.
    International Agency for Research on Cancer, France.
    Slimani, Nadia
    International Agency for Research on Cancer, France.
    Nicolas, Geneviève
    International Agency for Research on Cancer, France.
    Vignat, Jérôme
    International Agency for Research on Cancer, France.
    Wright, Anthony J A
    Food Databanks, Institute of Food Research, UK.
    Roe, Mark
    Food Databanks, Institute of Food Research, UK.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Finglas, Paul M
    Food Databanks, Institute of Food Research, UK.
    Critical evaluation of folate data in European and international databases: recommendations for standardization in international nutritional studies.2011In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 55, no 1, p. 166-180Article in journal (Refereed)
    Abstract [en]

    SCOPE: The objective was to perform an inventory and critical evaluation of folate data in selected European and international databases. The ultimate aim was to establish guidelines for compiling standardized folate databases for international nutritional studies.

    METHODS AND RESULTS: An ad hoc questionnaire was prepared to critically compare and evaluate folate data completeness, quantification, terminologies, and documentation of 18 European and international databases, and national fortification regulations. Selected countries participated in the European Prospective Investigation into Nutrition and Cancer project and European Food Information Resource Network (EuroFIR). Folate completeness was generally high. "Total folate" was the most common terminology and microbiological assay was the most frequently reported quantification method. There is a lack of comparability within and between databases due to a lack of value documentation, the use of generic or non-appropriate terminologies, folate value conversions, and/or lack of identification of synthetic folic acid.

    CONCLUSION: Full value documentation and the use of EuroFIR component identifiers and/or INFOODS tagnames for total folate ("FOL") and synthetic folic acid ("FOLAC"), with the additional use of individual folates, will increase comparability between databases. For now, the standardized microbiological assay for total folate and HPLC for synthetic folic acid are the recommended quantification methods.

  • 5.
    Büttner, Barbara E
    et al.
    Swedish University of Agricultural Sciences, Uppsala.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Domellöf, Magnus
    Umeå University.
    Hernell, Olle
    Umeå University.
    Öhlund, Inger
    Umeå University.
    Effect of type of heat treatment of breastmilk on folate content and pattern.2014In: Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 9, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms.

    MATERIALS AND METHODS: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57°C, 23 minutes; 62.5°C, 12 minutes) and a rapid high temperature treatment (heating to 73°C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography.

    RESULTS: The folate content in 38 untreated Swedish breastmilk samples was 150±46 nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78±7%) and tetrahydrofolate (22±7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures.

    CONCLUSIONS: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

  • 6.
    Büttner, Barbara E
    et al.
    Technische Universität München, Germany.
    Öhrvik, Veronica E
    Swedish University of Agricultural Sciences, Uppsala.
    Köhler, Peter
    German Research Center for Food Chemistry, Leibniz Institute Freising, Germany.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Rychlik, Michael
    Technische Universität München, Germany.
    Quantification of isotope-labeled and unlabeled folates and folate catabolites in urine samples by stable isotope dilution assay.2013In: International Journal for Vitamin and Nutrition Research, ISSN 0300-9831, E-ISSN 1664-2821, Vol. 83, no 2, p. 112-121Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Büttner, Barbara E
    et al.
    Technische Universität München, Germany.
    Öhrvik, Veronica E
    Swedish University of Agricultural Sciences, Uppsala.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Rychlik, Michael
    Technische Universität München, Germany.
    Quantification of isotope-labelled and unlabelled folates in plasma, ileostomy and food samples.2011In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 399, no 1, p. 429-439Article in journal (Refereed)
    Abstract [en]

    New stable isotope dilution assays were developed for the simultaneous quantitation of [(13)C(5)]-labelled and unlabelled 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, folic acid along with unlabelled tetrahydrofolic acid and 10-formylfolic acid in clinical samples deriving from human bioavailability studies, i.e. plasma, ileostomy samples, and food. The methods were based on clean-up by strong anion exchange followed by LC-MS/MS detection. Deuterated analogues of the folates were applied as the internal standards in the stable isotope dilution assays. Assay sensitivity was sufficient to detect all relevant folates in the respective samples as their limits of detection were below 0.62 nmol/L in plasma and below 0.73 μg/100 g in food or ileostomy samples. Quantification of the [(13)C(5)]-label in clinical samples offers the possibility to differentiate between folate from endogenous body pools and the administered dose when executing bioavailability trials.

  • 8. Finglas, P M
    et al.
    Wigertz, K
    Vahteristo, L
    Witthöft, Cornelia M.
    Institute of Food Research, Norwich Research Park, UK.
    Southon, S
    de Froidmont-Gortz, I
    Standardisation of HPLC techniques for the determination of naturally-occurring folates in food1999In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 64, no 2, p. 245-255Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to evaluate current in-house HPLC procedures for the determination of naturally-occurring folates in food, and to identify problem areas for further improvement. Five intercomparison studies were completed over the period 1990-1997 in which nine participants from six countries took part. Through careful validations and detailed discussions held at evaluation meetings, possible biases and sources of systematic error have been identified and reduced. The use of ascorbic acid and nitrogen flushing during extraction, sample clean-up using strong anion exchange columns, spectrophometrically calibrated standards and fluorescence detection are all recommended. Both in-house hog kidney and human plasma deconjugase enzymes gave similar results to the circulated common hog kidney enzyme which was prepared from fresh pig's kidneys. The most consistently reported values were for 5-CH3H4-PteGlu, and to a lesser extent, for H(4)PteGlu. Four candidate reference materials (CRM 121, wholemeal flour; CRM 421, milk powder; CRM 485, lyophilised mixed vegetables, and CRM 487, lyophilised pig's liver) have been proposed with both indicative values (mean +/- uncertainty) for 5-CH3H4-PteGlu in CRM 421 (0.25; +/- 0.02 mg/kg) and CRM 485 (2.14; +/- 0.42 mg/kg), and information values (mean; range) for 5-CH3H4-PteGlu in CRh4 121 (0.04; 0.03-0.08 mg/kg) and CRM 487 (2.6; 1.9-3.8 mg/kg), Certified values are also given for total folate by microbiological assay: CRM 121 (0.50; +/- 0.07 mg/kg), CRM 421 (1.42; +/- 0.14 mg/kg), CRM 485 (3.15; 0.28 mg/kg), and CRM 487 (13.4; 1.3 mg/kg). Average recovery of 5-CH3H4-PteGlu, added prior to extraction and deconjugation, was 91% (84-95%) for the four CRMs. The average within- and between-laboratory variations were 6 and 15% for the determination of 5-CH3H4-PteGlu by HPLC, and 9 and 18% for the determination of total folate by microbiological assay. These CRMs will be used for quality control of folate measurements for nutritional labelling, and validation of new techniques. Further methodology work is required for the HPLC analyses of folate forms other than 5-CH3H4-PteGlu. 

  • 9. Finglas, Paul M
    et al.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Vahteristo, Liisa
    Wright, Anthony J A
    Southon, Susan
    Mellon, Fred A
    Ridge, Brian
    Maunder, Peter
    Use of an oral/intravenous dual-label stable-isotope protocol to determine folic acid bioavailability from fortified cereal grain foods in women.2002In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 132, no 5Article in journal (Refereed)
    Abstract [en]

    Folic acid fortification, mandatory in the United States, is currently being considered by the UK. The hypothesis that the matrix of some cereal-product vehicles may result in low fortificant bioavailability was tested using a dual oral/intravenous (i.v.) isotopic-label approach, which was evaluated concurrently. Fifteen women received 225 microg oral folate (capsules, fortified white bread and fortified branflakes), mainly as folic acid labeled with (13)C on 6 carbons of the benzoyl ring ((13)C(6)-PteGlu), followed by i.v. injection of 100 microg folic acid labeled with (2)H on 4 hydrogens of the glutamic acid group ((2)H(4)-PteGlu). The urinary excretion ratio (UER) in intact folate of the percentage of labeled oral dose excreted divided by the percentage of i.v. dose excreted was used as the primary index of absorption. The geometric mean (95% confidence interval) UER for folic acid capsules was 3.68 (1.90, 7.14) at 24 h and 2.18 (1.24, 3.83) at 48 h. Because these were significantly in excess of 1.0, indicative of 100% absorption of the oral dose, it was concluded that oral and i.v. labeled folic acid are handled differently by the body and that "absolute" absorption cannot be calculated. Compared with the 48-h UER for folic acid capsules, the "relative" 48-h UER for white bread and branflakes was 0.71 and 0.37, respectively, indicating that some cereal-based vehicles may inhibit absorption of fortificant. However, even the validity of this "relative" approach is questioned.

  • 10. Forssén, K M
    et al.
    Jägerstad, M I
    Wigertz, K
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Folates and dairy products: a critical update.2000In: Journal of the American College of Nutrition (Print), ISSN 0731-5724, E-ISSN 1541-1087, Vol. 19, no 2 Suppl, p. 100S-110SArticle in journal (Refereed)
    Abstract [en]

    In recent years, folates have come into focus due to their protective role against child birth defects, for example, neural tube defects. In addition, folates may have a protective role to play against coronary heart disease and certain forms of cancer. During the last few years most countries have established increased recommended intakes of folates, for example, between 300-400 microg per day for adults. This review of folates in milk and dairy products compares some recent data based on high pressure liquid chromatography (HPLC) analyses and radioprotein-binding assays, with previous data based on microbiological assays. All three methods show similar ranges for folates in cow's milk, 5-10 microg per 100 g, the variation being due to seasonal variations. Data on folates in fermented milk (buttermilk and yogurt) are also similar for these methods. Different starter cultures, however, might explain some of the variations in folate content and folate forms. Most cheese varieties contain between 10 microg and 40 microg folate per kg, with slightly higher values for whey cheese. Ripened soft cheeses may contain up to 100 microg folate per 100 g. Most previous and recent studies using HPLC indicate that 5-methyl-tetrahydrofolate (5-methyl-THF) is the major folate form in milk, but more studies are needed concerning folate forms in other, especially fermented dairy products. Relatively new data on actual concentrations in different dairy products show folate-binding proteins (FBP) to occur in unprocessed milk, but also in pasteurised milk, spray-dried skim milk powder and whey. In contrast, UHT milk, fermented milk and most cheeses only contain low levels or trace amounts.

  • 11.
    Gurinovic, Mirjana A.
    et al.
    Univ Belgrade, Serbia.
    Oshaug, Arne
    Akershus Univ Coll, Norway.
    Finglas, Paul
    Inst Food Res, UK.
    Glibetic, Maria
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Hollman, Peter
    Wageningen Univ, Netherlands.
    Hulshof, Paul J.
    Wageningen Univ, Netherlands.
    Porubska, Janka
    VUP Food Res Inst, Slovakia.
    Tepsic, Jasna
    Capacity building in food composition data base in central and eastern Europe, Middle east and North Africa countries: Successful collaboration between EUROFIR and other networks2009In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 55, no Supplement 1, p. 565-565, article id P127-04Article in journal (Refereed)
  • 12. Gurinović, Mirjana
    et al.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Tepšić, J
    Ranić, M
    Hulshof, P J M
    Hollman, P C
    Porubska, J
    Gohar, A
    Debeljak-Martačić, J
    Petrović-Oggiano, G
    Novaković, R
    Glibetić, M
    Oshaug, A
    Capacity development in food composition database management and nutritional research and education in Central and Eastern European, Middle Eastern and North African countries.2010In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 64 Suppl 3, p. S134-S138Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Capacity development (CD) in food and nutrition is much more than formal training and includes human resource development, and organisational, institutional and legal framework development with the aim of enhancing nutrition-relevant knowledge and skills to support infrastructural development. The goal of the European Food Information Resource (EuroFIR) Network of Excellence has been to develop and integrate food composition data throughout Europe. EuroFIR joined forces in CD with the United Nations (UN) University and UN System Standing Committee on Nutrition, the Network for Capacity Development in Nutrition in Central and Eastern Europe, the Central and Eastern European Countries Food Data Systems network and with the Middle East and North African Capacity Building Initiative. The aim of this paper is to discuss an inventory of the status of food composition databases (FCDBs) and the training needs of compilers in non-EuroFIR countries in Central and Eastern Europe (CEE) and in the Middle East and North Africa (MENA), and to present the CD achieved through EuroFIR and other network collaborations.

    SUBJECTS/METHODS: Two online questionnaires were created addressing the FCDB status and specific training needs in countries of the targeted regions. Data were collected during 2006-2008 and then analysed. Subsequently, CD activities were organised.

    RESULTS: Contacts were established in 19 CEE and 7 MENA countries, of which several had national food composition tables, but no electronic versions. Education, training, workshops, networking and the sharing of experiences were uniformly requested. Subsequently, CD activities in EuroFIR were organised focussing on food composition courses, exchange visits, workshops and individual training for PhD students, junior scientists and other staff categories, as well as conferences linked to food composition research and food information. To facilitate CD activities, EuroFIR has signed a Memorandum of Understanding with the Czech Republic, Hungary, Slovenia, Croatia and Estonia.

    CONCLUSIONS: EuroFIR has created training activities that complement national activities. Collaboration with other networks has provided an overview of FCDB status and training needs, providing directions for CD activities in those countries. This provides a platform for new funding and further development and networking for CD, which would be conducive to European Commission objectives and public health strategies for CD.

  • 13. Havenaar, R
    et al.
    Verwei, M
    Olivares, A B
    Arkbage, K
    Ros, G
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Walker, C
    Carnovale, E
    Kariluoto, S
    Finglas, P
    Folate bioaccessibility from various food products studied in a dynamic in vitro gastrointestinal model.2003In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 133, no 11, p. 3862S-3863SArticle in journal (Refereed)
  • 14.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura University, Egypt.
    Schaller, Franziska
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Betaine, choline and folate content in different cereal genotypes2018In: Journal of Cereal Science, ISSN 0733-5210, E-ISSN 1095-9963, Vol. 80, p. 72-79Article in journal (Refereed)
    Abstract [en]

    The importance of dietary methyl donors, e.g. betaine, choline and folate, is increasingly being recognised. This study examined variations in methyl donor concentrations in different cereals grown in Sweden. Fourteen cereal samples, representing different genera and cultivars, were analysed using HPLC- UV/FLD. The content of methyl donors in the cereals varied significantly due to cereal genotype. Betaine content varied most, with 28 mg/100 g DM in oats and 176 mg/100 g DM in rye. Total choline varied less, with 67 mg/100 g DM in rye and 149 mg/100 g DM in naked barley. In wheat, the lowest concentration of folate with 36 mg/100 g DM was found, and the highest of 91 mg/100 g DM in barley. Esterified choline was the major contributor to total choline content (80e95%) in the cereals. Free choline was less abundant, ranging from 3 to 27mg/100g DM. 5-CHO-H4folate was the dominant folate form in all cereals, amounting to approx. 35e50% of the sum of folates, as determined after pre-column conversion. Due to the limited number of available cultivars, no interpretation regarding effects from cultivar can be made. In conclusion, the studied cereal genotypes are good sources of methyl donors, but concentrations show considerable variation between different cereals.

  • 15.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura University, Egypt.
    Shalaby, Mohamed T.
    Mansoura University, Egypt.
    Mohamed, Rasha A.
    Mansoura University, Egypt.
    Elwa, Ahmad M.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effect of a 12-Week Dietary Intervention with Folic Acid or Folate-Enhanced Foods on Folate Status in Healthy Egyptian Women2016In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, Vol. 7, p. 1339-1351Article in journal (Refereed)
    Abstract [en]

    The Egyptian government introduced wheat-flour fortification with iron and folic acid to reduce the incidence of neural tube defects, but suspended it for technical reasons. We previously developed novel legume foods with enhanced folate content. In this study, we investigated the efficacy of 12-week intervention with folate-en- hanced foods versus folic acid supplement in improving folate status in Egyptian women. A randomized, parallel intervention trial with two active groups (n = 19, n = 18) and one blinded control group (n = 20) was executed over 12 weeks. Volunteers received either germinated legume foods and orange juice (≈250 μg/d folate) or folic acid supplement (500 μg/d) or apple juice (0 μg/d folate). Folate status was assessed by erythrocyte and plasma folate and total homocysteine (tHcy) at day 0, and after 8 and 12 weeks of intervention. After 12 weeks, mean plasma folate increased by 14 (P < 0.0001) and 12 (P < 0.0001) nmoL in the folic acid and food group, respectively. Erythrocyte folate concentration increased in the folic acid group from 614 to 912 (P < 0.0001) and in the food group from 631 to 914 nmoL (P < 0.0001). After 12 weeks, 90% of subjects in the folic acid group and 70% in the food group had erythrocyte folate concentrations exceeding 906 nmol/L. tHcy concentration was decreased by 20% (P = 0.007) and 18% (P = 0.006) in the folic acid and food group, respectively, but remained unchanged in the control group during intervention. Folate-enhanced foods effectively improve folate status in women of reproductive age. These foods could be used as a complement to folic acid fortification 

  • 16.
    Hefni, Mohammed E.
    et al.
    Mansoura University, Egypt.
    Shalaby, Mohamed T
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Folate content in faba beans (Vicia faba L.) - effects of cultivar, maturity stage, industrial processing, and bioprocessing2015In: Food Science & Nutrition, E-ISSN 2048-7177, Vol. 3, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    Faba beans are an important source of folate and commonly consumed in Egypt. This study examined the effects of Egyptian industrial food processing (e.g., canning and freezing), germination, cultivar, and maturity stages on folate content, with the aim to develop a candidate functional canned faba bean food with increased folate content. The folate content in four cultivars of green faba beans ranged from 110 to 130 μg 100 g(-1) fresh weight (535-620 μg 100 g(-1) dry matter [DM]), which was four- to sixfold higher than in dried seeds. Industrial canning of dried seeds resulted in significant folate losses of ∼20% (P = 0.004), while industrial freezing had no effect. Germination of faba beans increased the folate content by >40% (P < 0.0001). A novel industrial canning process involving pregermination of dried faba beans resulted in a net folate content of 194 μg 100 g(-1) DM, which is 52% more than in conventional canned beans. The consumption of green faba beans should be recommended, providing ∼120 μg dietary folate equivalents per 100 g/portion.

  • 17.
    Hefni, Mohammed E.
    et al.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Effect of germination and subsequent oven-drying on folate content in different wheat and rye cultivars2012In: Journal of Cereal Science, ISSN 0733-5210, E-ISSN 1095-9963, Vol. 56, no 2, p. 374-378Article in journal (Refereed)
    Abstract [en]

    Cereals are recognised as an important food source of folate, and germinated cereals are reported to contain even more folate. This study examined the effects of germination and oven-drying on folate content in different wheat and rye cultivars. The native folate content in four wheat cultivars ranged from 23 to 33 μg/100 g dry matter (DM) and that in six rye cultivars from 31 to 39 μg/100 g DM. Mean folate content in rye was 25% higher than in wheat. Germination of both cereals resulted in a 4- to 6-fold increase in folate content, depending on cultivar and duration of germination. The highest folate content in both cereals was found after 96 h of germination and was 181 μg/100 g DM for cv. Kaskelott (rye) and 155 μg/100 g DM for cv. Kosack (wheat). Germination increased the amount of 5-CH 3-H 4folate in both cereals from 45 to 75%. Oven-drying of germinated wheat grains (for 48 and 72 h) at 50 °C did not affect the folate content. In conclusion, germination increases the folate content in wheat and rye cultivars, while subsequent oven-drying does not affect the folate content. Germination can therefore be recommended for producing bakery ingredients with increased folate content. © 2012 Elsevier Ltd.

  • 18.
    Hefni, Mohammed E.
    et al.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Egyptian Legume and Cereal Foods: Traditional and New Methods for Processing2016In: Mediterranean Foods: Composition and Processing / [ed] Rui M. S. Cruz, Margarida C. Vieira, CRC Press, 2016, p. 102-120Chapter in book (Refereed)
  • 19.
    Hefni, Mohammed E.
    et al.
    Swedish University of Agricultural Sciences, Uppsala;Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Enhancement of the folate content in Egyptian pita bread.2012In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 56Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Egypt has a high incidence of neural tube defects related to folate deficiency. One major food source for folate is pita (baladi) bread, which is consumed daily. Bioprocessing (e.g. germination) has been reported to increase the folate content in cereals. The aim was to produce pita bread with increased folate content using germinated wheat flour (GWF).

    METHODS: Prior to milling the effects of germination and drying conditions on folate content in wheat grains were studied. Pita bread was baked from wheat flour substituted with different levels of GWF. The folate content in dough and bread and rheological properties of dough were determined.

    RESULTS: Germination of wheat grains resulted in, depending on temperature, 3- to 4-fold higher folate content with a maximum of 61 µg/100 g DM (dry matter). The folate content in both flour and bread increased 1.5 to 4-fold depending on the level of flour replacement with GWF. Pita bread baked with 50% sieved GWF was acceptable with respect to colour and layer separation, and had a folate content of 50 µg/100 g DM compared with 30 µg/100 g DM in conventional pita bread (0% GWF).

    CONCLUSION: Using 50% GWF, pita bread with increased folate content, acceptable for the Egyptian consumer, was produced. Consumption of this bread would increase the average daily folate intake by 75 µg.

  • 20.
    Hefni, Mohammed E.
    et al.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Folate content in processed legume foods commonly consumed in Egypt2014In: Lebensmittel-Wissenschaft + Technologie, ISSN 0023-6438, E-ISSN 1096-1127, Vol. 57, no 1, p. 337-343Article in journal (Refereed)
    Abstract [en]

    Industrial food processing and household cooking are reported to affect folate content. This study examined the effects of industrial and household processing methods on folate content in traditional Egyptian foods from faba beans (Vicia faba) and chickpeas (Cicer arietinum). Overnight soaking increased folate content by ∼40–60%. Industrial canning including soaking, blanching and retorting did not affect folate content (p = 0.11) in faba beans, but resulted in losses of ∼24% (p = 0.0005) in chickpeas. Germination increased folate content 0.4–2.4-fold. Household preparation increased the folate content in germinated faba bean soup (nabet soup) one-fold and in bean stew (foul) by 20% (p < 0.0001). After deep-frying of falafel balls made from soaked faba bean paste, losses of 10% (p = 0.2932) compared with the raw faba beans were observed. The folate content (fresh weight) in the traditional Egyptian foods foul and falafel and in the beans in nabet soup was 30 ± 2, 45 ± 2 and 56 ± 6 μg/100 g, respectively. The traditional Egyptian foods foul, falafel and nabet soup are good folate sources and techniques like germination and soaking, which increase the folate content, can therefore be recommended.

  • 21.
    Hefni, Mohammed E.
    et al.
    Swedish University of Agricultural Sciences ; Mansoura Univ, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Increasing the folate content in Egyptian baladi bread using germinated wheat flour2011In: Lebensmittel-Wissenschaft + Technologie, ISSN 0023-6438, E-ISSN 1096-1127, Vol. 44, no 3, p. 706-712Article in journal (Refereed)
    Abstract [en]

    The main objective of this study was to increase the folate content in Egyptian baladi bread using germinated wheat flour (GWF). The effect of germination temperature and drying conditions on the folate content of wheat grains was studied. Wheat flour was substituted with unsieved and sieved GWF at different levels and the effects on folate content and the rheological properties of dough were determined. Germination of wheat grains resulted in a 3- to 4-fold higher folate content depending on the germination temperature. Maximum folate content (61 mu g/100 g dry matter (DM)) occurred at 30 degrees C. Drying did not affect folate content in germinated grains. After replacement with GWF, folate content in both flour and bread increased 1.5- to 4-fold depending on the level of replacement. Rheological properties of dough were adversely affected by increasing replacement level (as determined by farinograph). While the folate content in bread was as high as 66 mu g/100 g DM at complete replacement of flour with sieved GWF, the bread was dark and layers were not separated. After replacement of half of the flour with sieved GWF (50 g/100 g), the baladi bread was acceptable with respect to colour and layer separation. The folate content in this bread was 50 mu g/100 g DM, compared with 30 mu g/100 g DM in bread without GWF (0 g/100 g). (c) 2010 Elsevier Ltd. All rights reserved.

  • 22.
    Hefni, Mohammed E.
    et al.
    Swedish Univ Agr Sci ; Mansoura Univ, Egypt.
    Öhrvik, Veronica
    Swedish University of Agricultural Sciences.
    Tabekha, Mohamed
    Mansoura Univ, Egypt.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Folate content in foods commonly consumed in Egypt2010In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 121, no 2, p. 540-545Article in journal (Refereed)
    Abstract [en]

    The folate content in some Egyptian foods was determined using RP-HPLC-FL. Trienzyme treatment was used for legumes, dienzyme treatment for cereals and starchy vegetables, and monoenzyme treatment for vegetables and fruits. The highest folate content (633 mu g/100 g) was found in dried Jew's mellow due to low water content, followed by legumes (e.g. 150 mu g/100 g for chick peas) and leafy vegetables (100 mu g/100 g). For other foods, folate content ranged from 10-90 mu g/100 g. In all foods, the predominant folate form was 5-CH(3)-H(4)folate, except for dried Jew's mellow, which contained more than 80% 10-HCO-PteGlu. Using folate data from our own analyses and food tables and food consumption data, the dietary folate intake per capita in Egypt was estimated. However, representative and validated food composition data for folate in Egyptian foods are needed for estimating and evaluating the adequacy of the population's folate intake. (C) 2009 Elsevier Ltd. All rights reserved.

  • 23.
    Hollman, Peter C. H.
    et al.
    RIKILT Inst Food Safety, Netherlands ;Wageningen Univ, Netherlands.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Busstra, Maria C.
    Wageningen Univ, Netherlands.
    Elburg, Lucy
    Wageningen Univ, Netherlands.
    Hulshof, Paul
    Wageningen Univ, Netherlands.
    Training aspects in the use and production of food composition databases. The EuroFIR experience2009In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 113, no 3, p. 842-845Article in journal (Refereed)
    Abstract [en]

    An increasing number of national food databases have been published on the internet. However, these internet databases can only be searched individually, and the data have been compiled at a national level, resulting in incompatibilities. To resolve these problems, the Network of Excellence EuroFIR develops an internet based platform for online access to various national authoritative sources of food composition data in Europe. Training is essential for its use, and for the development of harmonised procedures of data production, evaluation, compilation, and retrieval. The training program developed within EuroFIR consists of individual training, supported by exchange grants, and a collection of workshops and training courses. Supportive E-learning modules are under construction. Procedures for the evaluation of each training activity have been made to measure its efficacy, and to learn about new training needs. Attention is given to special training needs of compilers in central and eastern European countries. (C) 2008 Elsevier Ltd. All rights reserved.

  • 24.
    Jastrebova, Jelena
    et al.
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Grahn, Anders
    ChromTech.
    Svensson, Ulla
    Procordia Food.
    Jagerstad, Margaretha
    Swedish University of Agricultural Sciences.
    HPLC determination of folates in raw and processed beetroots2003In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 80, no 4, p. 579-588Article in journal (Refereed)
    Abstract [en]

    A sensitive HPLC method with fluorescence detection and gradient elution has been developed for the determination of folates in vegetables. The method involved extraction of folates from food matrix by heat treatment, deconjugation of folate polyglutamates to monoglutamates by incubation with hog kidney conjugase and purification of food extracts by solid-phase extraction with strong-anion exchange cartridges. The chromatographic separation of folates was achieved on Zorbax SB C-8 column, which was found to be superior over conventional C-18 column in terms of selectivity and sensitivity. Validation of the method included linearity tests, the addition of standard folates for the determination of recovery, repeatability and stability tests. The method developed was applied to analysis of raw and processed beetroots; 5-methyltetrahydrofolate was found to be the main folate form in beetroots. Cultivar differences and growing conditions were found to have a pronounced effect on the folate content in beetroots. Processing resulted in considerable losses of folates, whereas losses during storage appeared to be moderate.

  • 25.
    Johansson, Madelene
    et al.
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Bruce, Ake
    National Food Administration.
    Jägerstad, Margaretha
    Swedish University of Agricultural Sciences.
    Study of wheat breakfast rolls fortified with folic acid: The effect on folate status in women during a 3-month intervention2002In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 41, no 6, p. 279-286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Folate has come into focus due to its protective role against child birth defects such as neural tube defects (NTD). Swedish authorities recommend all fertile women to increase their folate intake to 400 microg/day by eating folate-rich foods. Because not all women follow these recommendations, there is a discussion today about whether Sweden should introduce folic acid fortification in wheat flour and sifted rye flour. This decision needs knowledge about the bioavailability of folic acid from fortified foods.

    AIM OF THE STUDY: To investigate effects of two folic acid fortification levels on folate status in healthy female volunteers and to study the folic acid stability during the baking procedure and storage of the fortified breakfast rolls.

    METHOD: Twenty-nine healthy women were recruited. Folic acid-fortified wheat breakfast rolls were baked with the purpose to contain 200 microg folic acid/roll (roll L) and 400 microg folic acid/roll (roll H). Fourteen women were given one roll/day of roll L (group L) and 15 one roll/day of roll H (group H) during 12 weeks of intervention. Fasting venous blood samples were collected on days 0, 30, 60 and 90. Serum homocysteine concentrations were determined using an immunoassay. Serum and erythrocyte folate concentrations were analysed using a protein-binding assay with fluorescent quantification. The folic acid concentration in the breakfast rolls was analysed by HPLC on days 0, 30, 60 and 90. Total folate concentration was measured with microbiological assay on day 45.

    RESULTS: Group L Group L had initially an average erythrocyte folate concentration of 577 +/- 93 nmol/L. After 90 days of intervention, an increase of 20 % (p < 0.05) was observed. At day 0, mean serum folate concentrations were 16.9 +/- 4.3 nmol/L. The mean serum folate concentrations increased by 30 % (p < 0.001) after 90 days. At day 0, mean serum homocysteine concentrations were 9.1 +/- 2.0 micromol/L, which decreased by 20 % (p < 0.01) after 30 days. Group H Group H had an initial erythrocyte folate concentration of 784 +/- 238 nmol/L. After 90 days, an increase of 26 % (p < 0.05) was observed. Serum folate increased at least 22 % after 30 days, from a level of 18.7 +/- 4.8 nmol/L at day 0. Thereafter, all women of group H had serum concentrations at or above the upper limit of quantification (23 nmol/L). At day 0, mean serum homocysteine concentrations were 8.4 +/- 1.7 micromol/L, which decreased by 16 % (p < 0.05) after 30 days. The baking procedure resulted in 20-25 % loss of fortified folic acid in the rolls used in the present study. The size of the rolls affected the retention of folic acid during baking. No significant loss was seen in folic acid concentration in the rolls during the intervention period.

    CONCLUSION: The present study showed that in healthy women, subjected to a 12-week intervention with breakfast rolls fortified with either 166 microg or 355 microg folic acid, serum homocysteine concentration decreased (p < 0.05) and erythrocyte folate increased (p < 0.05). The lower level of fortification seems to be sufficient to improve the folate status. Together with the average daily intake of natural folates, these women reach the recommended intake of 400 microg/day. Folic acid is stable in fortified bread for 90 days storage at -20 degrees C.

  • 26.
    Maunder, Peter
    et al.
    University of Exeter, UK.
    Finglas, Paul M.
    Norwich Laboratory, UK.
    Mallet, Anthony I.
    University of London, UK.
    Mellon, Fred A.
    Norwich Laboratory, UK.
    Razzaque, M. Aaqib
    University of London, UK.
    Ridge, Brian
    University of Exeter, UK.
    Vahteristo, Liisa
    Norwich Laboratory, UK.
    Witthöft, Cornelia M.
    Norwich Laboratory, UK.
    The synthesis of folic acid, multiply labelled with stable isotopes, for bio-availability studies in human nutrition1999In: Journal of the Chemical Society-Perkin Transactions 1, ISSN 0300-922X, no 10, p. 1311-1323Article in journal (Refereed)
    Abstract [en]

    Two different methods for the synthesis of folic acid, which are suitable for the incorporation of compounds multiply labelled with stable isotopes, are described. The first method is based on the use of a novel reductive amination to link 2-acetylamino-4-hydroxy-6-formylpteridine with p-aminobenzoyl-L-glutamic acid. The second method is based on the penultimate formation of an amide bond between N-2-acetyl-N-10-trifluoroacetylpteroic acid and dimethyl L-glutamate. Both methods have been used to transform [C-13(6)]aniline into folic acid, labelled with [C-13(6)] in the p-aminobenzoate moiety, and [3,3,4,4-H-2(4)]-L-glutamic acid into folic acid, labelled with [H-2(4)] in the glutamate moiety. Doubly labelled [C-13(6), H-2(4)]-p-aminobenzoyl-L-glutamate has also been prepared by the former method.

  • 27.
    Nicolas, Geneviève
    et al.
    International Agency for Research on Cancer, France.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Vignat, Jérôme
    International Agency for Research on Cancer, France.
    Knaze, Viktoria
    International Agency for Research on Cancer, France.
    Huybrechts, Inge
    International Agency for Research on Cancer, France.
    Roe, Mark
    Institute of Food Research, Norwich Research Park, UK.
    Finglas, Paul
    Institute of Food Research, Norwich Research Park, UK.
    Slimani, Nadia
    International Agency for Research on Cancer, France.
    Compilation of a standardised international folate database for EPIC.2016In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 193, p. 134-140Article in journal (Refereed)
    Abstract [en]

    This paper describes the methodology applied for compiling an "international end-user" folate database. This work benefits from the unique dataset offered by the European Prospective Investigation into Cancer and Nutrition (EPIC) (N=520,000 subjects in 23 centres). Compilation was done in four steps: (1) identify folate-free foods then find folate values for (2) folate-rich foods common across EPIC countries, (3) the remaining "common" foods, and (4) "country-specific" foods. Compiled folate values were concurrently standardised in terms of unit, mode of expression and chemical analysis, using information in national food composition tables (FCT). 43-70% total folate values were documented as measured by microbiological assay. Foods reported in EPIC were either matched directly to FCT foods, treated as recipes or weighted averages. This work has produced the first standardised folate dataset in Europe, which was used to calculate folate intakes in EPIC; a prerequisite to study the relation between folate intake and diseases.

  • 28.
    Pavlovic, Mirjana
    et al.
    Univ Belgrade, Serbia.
    Witthöft, Cornelia M.
    Swedish Univ Agr Sci.
    Hollman, Peter
    Wageningen Univ, Netherlands.
    Hulshof, Paul J. M.
    Wageningen Univ, Netherlands.
    Glibetic, Maria
    Univ Belgrade, Serbia.
    Porubska, Janka
    VUP Food Res Inst, Slovakia.
    Pepping, Fre
    Wageningen Univ, Netherlands.
    Oshaug, Arne
    Akershus Univ Coll, Norway.
    Training and capacity building in central and eastern Europe through the EuroFIR and CEE networks2009In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 113, no 3, p. 846-850Article in journal (Refereed)
    Abstract [en]

    Capacity building in food and nutrition aims to enhance knowledge and support infrastructural development in this field. International Network of Food Data Systems (INFOODS) was established on the basis of the recommendations of an international group convened under the auspices of the United Nations University (UNU). The European Food Information Resource Network (EuroFIR, Network of Excellence) aims to develop and integrate food composition data through Europe including CEE countries. EuroFIR, joined forces with the United Nations University/UN System Standing Committee on Nutrition, in capacity building. Inventories have been initiated by EuroFIR on food composition data base status and on capacity development needs. The inventories showed that many activities are already ongoing, providing a good potential for developments needed. Substantial differences exist between the countries, including lack of understanding about the concepts and what quality implies. Assessing the quality, frequency of the capacity development activities and the number of staff trained is needed. Several countries lacked adequate information: 6 of 8 had established Food Composition Databases, but none had electronic versions of the Food Composition Databases. Most had national databases, but needs for additional equipment seems considerable. Education, training, workshops, networking and sharing of experiences were cross-cutting themes for most countries. It is concluded that capacity development is a long-term, continuing process, with policies, plans, and activities and should have national priority. Special attention should be given to the capacity development dimensions generated by global and European strategies. Capacity development networks would be important tools in addressing present and future needs in various Countries. The EuroFIR training and exchange program is a valuable tool in achieving this. (C) 2008 Elsevier Ltd. All rights reserved.

  • 29.
    Röös, Elin
    et al.
    Swedish University of Agricultural Sciences, Uppsala.
    Karlsson, Hanna
    Swedish University of Agricultural Sciences, Uppsala.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences, Uppsala.
    Sundberg, Cecilia
    Swedish University of Agricultural Sciences, Uppsala.
    Evaluating the sustainability of diets-combining environmental and nutritional aspects2015In: Environmental Science and Policy, ISSN 1462-9011, E-ISSN 1873-6416, Vol. 47, p. 157-166Article in journal (Refereed)
    Abstract [en]

    This study examined two methods for jointly considering the environmental impact and nutritional quality of diets, which is necessary when designing policy instruments promoting sustainable food systems. Both methods included energy content and 18 macro- and micronutrients in the diet, the climate impact, land use and biodiversity damage potential. In Method 1, the content of different nutrients in the diet was normalised based on recommended intake or upper levels for average daily intake and presented together with the environmental impacts, which were normalised according to estimated sustainable levels. In Method 2, the nutritional quality of different diets was considered by calculating their nutrient density score, and the environmental impact was then expressed per nutrient density score. Three diets were assessed; a diet corresponding to Nordic recommendations, the current average Swedish diet and a lifestyle Low Carbohydrate-High Fat (LCHF) diet. Method 1 clearly showed that the climate impact was far beyond the sustainable level for all diets, while land use was within the sustainability limit for the recommended diet, but not the other two. Comparisons based on nutrient density scores depended on the score used, but the current and LCHF diets had more impact than the recommended diet (less livestock products) for all but one score. Over- and under-consumption of nutrients were clearly shown by Method 1 but not possible to distinguish with Method 2, as normalisation was not possible, making it difficult to evaluate the absolute scale of the impacts when nutrient density scores were used. For quantitative information on the environmental and nutritional impacts of diets as support in decision-making processes, it is important that data presentation is transparent. There is limited value in reducing results to a low number of indicators that are easy to read, but difficult to interpret, e.g. nutrient density score. Method 1 allows combined assessment of diets regarding environmental impact and nutritional intake and could be useful in dietary planning and in development of dietary recommendations and other policy instruments to achieve more sustainable food systems. © 2014 Elsevier Ltd.

  • 30.
    Sonesson, Ulf
    et al.
    SP Technical Research Institute of Sweden.
    Davis, Jennifer
    SP Technical Research Institute of Sweden.
    Flysjo, Anna
    Arla Foods Amba, Denmark.
    Gustaysson, Jenny
    SP Technical Research Institute of Sweden.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Swedish University of Agricultural Sciences.
    Protein quality as functional unit: A methodological framework for inclusion in life cycle assessment of food2017In: Journal of Cleaner Production, ISSN 0959-6526, E-ISSN 1879-1786, Vol. 140, no Special Issue, Part 2, p. 470-478Article in journal (Refereed)
    Abstract [en]

    In order to. develop more sustainable food systems, there is a need to find methods that simultaneously consider environmental impacts and nutritional benefits. The purpose of this, study was to develop a functional unit to be used in LCA of foods that builds on the nutritional value of food products. We used the content and quality of proteins as a basis, and included dietary context as part of our method, since the nutritional value of a nutrient depends on the total dietary intake. Our method uses the digestible intake of the nine essential amino acids in the product and relates these values to the equivalent total dietary intake of the same amino acids. We also employed simpler functional units such as "gram (g) protein" and "g digestible protein." We quantified the functional units for three dietary contexts and applied it on LCA results for bread, chicken fillet, minced pork, minced beef, milk and pea soup. The results showed that the relative differences between products changed when using a protein-based functional unit, with the largest change occurring when going from mass as the functional unit to g protein. By introducing protein digestibility, the systematic under-valuation of the animal products was partly avoided with little additional effort. The most advanced functional unit affected the results compared to the mass-based functional unit most, but required significantly more data. The impact of dietary context was smaller than expected; hence, it might be possible to simplify the inclusion of dietary context by using aggregated descriptions of diets. The method presented is valuable for adding an important aspect of nutrition (protein quality and content) to the LCA results of single products, but there is a large scope for development. (C) 2016 Elsevier Ltd. All rights reserved.

  • 31.
    Strålsjö, Lena
    et al.
    Swedish University of Agricultural Sciences.
    Arkbåge, Karin
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Jägerstad, Margaretha
    Swedish University of Agricultural Sciences.
    Evaluation of a radioprotein-binding assay (RPBA) for folate analysis in berries and milk2002In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 79, no 4, p. 525-534Article in journal (Refereed)
    Abstract [en]

    This study aimed to optimise a commercial radioprotein-binding assay (RPBA), routinely used for clinical samples, for folate quantification in foods containing mainly 5-CH3-H(4)folate. The assay was modified using external calibration with 5-CH3-H(4)folate in a lower concentration range diluted in food extraction buffer, rather than the buffer with human serum albumin (HSA) provided by the kit. We evaluated the modified RBPA on some selected food products; milk, whey powder, rose hips, strawberries and European certified reference materials (CRM 421, 485) and the adjustments did not affect the assay negatively. Performance parameters included control of selectivity, absence of matrix effects, recoveries of 94-113%, precision of 1-6 CV% (intra-assay) and 5-9 CV% (inter-assay). Folate concentrations in berries and milk, obtained by the modified RPBA were also compared with other quantification methods such as HPLC and MA. The optimised RPBA was found to be a quick and inexpensive complement to HPLC methods, reliable for folate quantification in foods such as milk and berries that contain mainly 5-CH3-H(4)folate. (C) 2002 Elsevier Science Ltd. All rights reserved.

  • 32. Strålsjö, Lena M
    et al.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Sjöholm, Ingegerd M
    Jägerstad, Margaretha I
    Folate content in strawberries (Fragaria x ananassa): effects of cultivar, ripeness, year of harvest, storage, and commercial processing.2003In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 51, no 1, p. 128-133Article in journal (Refereed)
    Abstract [en]

    Folate concentrations in strawberries and folate retention during storage and commercial processing of strawberries were investigated. No previous study has focused on the effects of cultivar, ripeness, and year of harvest of strawberries with respect to the folate content. This study showed the folate concentration in strawberries to significantly depend on all of these different factors. Total folate was quantified using a modified and validated radioprotein-binding assay with external calibration (5-CH(3)-H(4)folate). Folate content in 13 different strawberry cultivars varied from 335 microg/100 g of dry matter (DM) for cv. Senga Sengana to 644 microg/100 g of DM for cv. Elsanta. Swedish harvests from 1999 and 2001 yielded higher folate concentrations than did the harvest from 2000, and the grade of ripeness affected the folate content in strawberries. This study indicated high folate retention in intact berries during storage until 3 or 9 days at 4 degrees C (71-99%) and also in most tested commercial products (79-103%). On the basis of these data fresh strawberries as well as processed strawberry products are recommended to be good folate sources. For instance, 250 g (fresh weight) of strawberries ( approximately 125 microg of folate) supplies approximately 50% of the recommended daily folate intake in various European countries (200-300 microg/day) or 30% of the U.S. recommendation (400 microg/day).

  • 33.
    Strålsjö, Lena
    et al.
    Swedish University of Agricultural Science.
    Åhlin, Hanna
    Swedish University of Agricultural Science.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Science.
    Jastrebova, Jelena
    Swedish University of Agricultural Science.
    Folate determination in Swedish berries by radioprotein-binding assay (RPBA) and high performance liquid chromatography (HPLC)2003In: European Food Research and Technology, ISSN 1438-2377, E-ISSN 1438-2385, Vol. 216, no 3, p. 264-269Article in journal (Refereed)
    Abstract [en]

    Folate content in berries and the effect of cultivar on folate content in strawberries were investigated using a modified radioprotein-binding assay (RPBA) combined with solid phase extraction (SPE). With an SPE step prior to quantification the matrix effects in the RPBA assay were minimised. HPLC quantification was used to compare and characterise individual folate forms. High correlation (r = 0.9796) was shown and the mean difference between the RPBA and HPLC method was 6.7 4.8 mug/100 g. The predominating folate form was 6S-5-CH3-H-4-folate in all tested berries (>95%). Therefore, this biologically active folate form (6S-5-CH3-H(4)folate) must be chosen as calibrant because the RPBA response of the synthetic equimolar mixture of R- and S-diastereomers (6R,S-5-CH3-H(4)folate) was considerably higher, about 30%. The folate content in nine selected Swedish berries varied from 11 to 96 mug/100 g (fresh weight) and the highest folate content was found in rose hips (96 mug/100 g) and strawberries (74 mug/100 g). Moderate folate sources were raspberry (46 mug/100 g) and sea buckthorn (39 mug/100 g), whereas all other tested berries contained about 20 mug of folate/100 g or less. In strawberries, folate content varied significantly among eight different cultivars from 73 mug/100 g (Lina) to 99 mug/100 g (Melody).

  • 34. Vahteristo, L
    et al.
    Finglas, P M
    Witthöft, Cornelia M.
    Justus Liebig-Universität, Germany.
    Wigertz, K
    Seale, R
    deFroidmontGortz, I
    Third EU MAT intercomparison study on food folate analysis using HPLC procedures1996In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 57, no 1, p. 109-111Article in journal (Refereed)
    Abstract [en]

    Three samples (milk powder, lyophilized pig's liver and wholemeal flour), a 5-methyltetrahydrofolic acid (5-MTHF) calibrant and two deconjugase enzymes (purified hog kidney and human plasma) were circulated to three laboratories taking part in the study. The objectives were to optimize the deconjugation step in these foods and to improve the between-laboratory agreement in HPLC results for folates. The predominant natural folate form in milk powder was 5-MTHF, together with appreciable amounts of folic acid. In pig's liver 5-MTHF was found to represent about one-third of the total folate content found. For these two foods, results from one laboratory of the sum of the folate vitamers agreed favourably with the microbiological data. 5-MTHF was most successfully determined by all three laboratories. There was little or no agreement found for the other folate vitamers detected. Copyright (C) 1996 Elsevier Science Ltd

  • 35.
    Van Guelpen, B.
    et al.
    Umeå University.
    Hultdin, J.
    Umeå University.
    Johansson, I.
    Umeå University.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Weinehall, L.
    Umeå University ; National Public Health Institute.
    Eliasson, M.
    Umeå University ; Sunderby Hospital.
    Hallmans, G.
    Umeå University.
    Palmqvist, R.
    Umeå University.
    Jansson, J.-H.
    Umeå University ; Skellefteå Hospital.
    Winkvist, A.
    University of Gothenburg.
    Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, no 2, p. 182-195Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI).

    DESIGN: Nested case-referent study with up to 13 years of follow-up.

    SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment.

    SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data.

    RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations.

    CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.

  • 36. Van Guelpen, Bethany
    et al.
    Hultdin, Johan
    Johansson, Ingegerd
    Stegmayr, Birgitta
    Hallmans, Göran
    Nilsson, Torbjörn K
    Weinehall, Lars
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Palmqvist, Richard
    Winkvist, Anna
    Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake.2005In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 36, no 7, p. 1426-1431Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms.

    METHODS: Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort.

    RESULTS: Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype.

    CONCLUSIONS: The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.

  • 37. Verwei, M
    et al.
    Arkbåge, K
    Groten, J P
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    VandenBerg, H
    Havenaar, R
    The effect of folatebinding proteins on bioavailability of folate from milk products2005In: Trends in Food Science & Technology, ISSN 0924-2244, E-ISSN 1879-3053, Vol. 16, no 6-7, p. 307-310Article in journal (Refereed)
  • 38. Verwei, Miriam
    et al.
    Arkbåge, Karin
    Havenaar, Robert
    van den Berg, Henk
    Schaafsma, Gertjan
    SLU.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model.2003In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 133, no 7, p. 2377-2383Article in journal (Refereed)
    Abstract [en]

    Dairy products are a potential matrix for folate fortification to enhance folate consumption in the Western world. Milk folate-binding proteins (FBP) are especially interesting because they seem to be involved in folate bioavailability. In this study, folate bioaccessibility was investigated using a dynamic computer-controlled gastrointestinal model [TNO gastrointestinal model (TIM)]. We used both ultrahigh temperature (UHT)-processed milk and pasteurized milk, differing in endogenous FBP concentrations and fortified with folic acid or 5-methyltetrahydrofolate (5-CH(3)-H(4)folate). To study FBP stability during gastrointestinal passage and the effect of additional FBP on folate bioaccessibility, FBP-fortified UHT and pasteurized milk products were also tested. Folate bioaccessibility and FBP stability were measured by taking samples along the compartments of the gastrointestinal model and measuring their folate and FBP concentrations. Folate bioaccessibility from folic acid-fortified milk products without additional FBP was 58-61%. This was lower (P < 0.05) than that of the 5-CH(3)-H(4)folate-fortified milk products (71%). Addition of FBP reduced (P < 0.05) folate bioaccessibility from folic acid-fortified milk (44-51%) but not from 5-CH(3)-H(4)folate-fortified milk products (72%). The residual FBP levels in the folic acid- and 5-CH(3)-H(4)folate-fortified milk products after gastrointestinal passage were 13-16% and 0-1%, respectively, of the starting amounts subjected to TIM. In conclusion, milk seems to be a suitable carrier for folate, because both folic acid and 5-CH(3)-H(4)folate are easily released from the matrix and available for absorption. However, our results suggest that folic acid remains partly bound to FBP during passage through the small intestine, which reduces the bioaccessibility of folic acid from milk in this model.

  • 39.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Analytical Methods to Assess the Bioavailability of Water-Soluble Vitamins in Food: Exemplified by Folate2011In: Fortified Foods with Vitamins: Analytical Concepts to Assure Better and Safer Products / [ed] Michael Rychlik, Wiley-VCH Verlagsgesellschaft, 2011, 1, p. 21-36Chapter in book (Other academic)
    Abstract [en]

    This chapter reviews briefly analytical methods and models for the determination of in vivo folate bioavailability. Advantages and limitations of models are discussed and recent data on the bioavailability of native food folates and folic acid fortificant are summarized.

  • 40.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Vitamins: Folates2011In: Encyclopedia of Dairy Sciences / [ed] John W. Fuquay; Patrick F. Fox; Paul L. H. McSweeney, Academic Press, 2011, 2, p. 678-686Chapter in book (Other academic)
    Abstract [en]

    Folate is one of the water-soluble B-vitamins and is an essential micronutrient required as a coenzyme in the human body’s one-carbon metabolism. A good folate status is linked to several health benefits, for example, reduced risk for neural tube defects, other malformations during pregnancy, and coronary heart disease. Leafy green vegetables are rich in folate, while dairy products are considered as only moderate folate sources. Processing and storage can affect folate content. The average intake of dietary folate, as epidemiologic data show, is half the recommendation in countries with no mandatory fortification policy. This article aims to briefly present the chemistry, physiological functions, and health-protective role of folates. A short overview on analytical methods is given. Thereafter, data on the folate content of milk and dairy products are presented, and the effects of processing are discussed briefly. With emphasis to dairy products, research findings in connection with folate bioavailability and folic acid fortification are summarized.

  • 41.
    Witthöft, Cornelia M.
    et al.
    Sveriges lantbruksuniversitet, Uppsala.
    Arkbåge, Karin
    Johansson, Madelene
    Lundin, Eva
    Berglund, Gerd
    Zhang, Jie-Xian
    Lennernäs, Hans
    Dainty, Jack R
    Folate absorption from folate-fortified and processed foods using a human ileostomy model.2006In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 95, no 1, p. 181-187Article in journal (Refereed)
    Abstract [en]

    Data on folate absorption from food from validated human studies using physiological folate doses are still needed to estimate dietary requirements and to formulate recommendations. The aim of the present work was to study the effects from fortified and processed foods on folate absorption in ileostomy volunteers (n 9) using the area under the plasma concentration curve (AUC) and kinetic modelling. Using a standardized single-dose protocol, dairy products fortified with a candidate fortificant (6S)-5-methyltetrahydrofolate ((6S)-5-CH3-H4folate), folic acid-fortified bread and a dessert crème containing natural yeast folate polyglutamates were compared with folate supplements. Absorbed folate was estimated by AUC and a kinetic model, and non-absorbed folate by ileostomal folate excretion. Median apparent absorption from test foods ranged from 55 to 86 %. Added folate-binding proteins (FBP) significantly reduced folate absorption from dairy products, as in the absence of FBP, AUC-dose-corrected ratios were increased and ileal folate excretion decreased. After in vivo gastrointestinal passage of dairy products containing FBP, up to 43 % of the ingested FBP was found in ileostomal effluent. Folate absorption was similar for (6S)-5-CH3-H4folate fortificant from fermented milk and for folic acid from fortified bread. Folic acid, ingested as food fortificant in bread, was significantly less absorbed compared with an isolated supplement. We conclude that all tested foods were suitable matrices for folate fortification. However, dairy products, fortified with the new candidate fortificant (6S)-5-CH3-H4folate, are suitable if no active FBP is present.

  • 42.
    Witthöft, Cornelia M.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hefni, Mohammed E.
    Mansoura University, Egypt.
    Folic acid and Folates: Physiology and Health Effects2016In: The Encyclopedia of Food and Health / [ed] Caballero, B., Finglas, P., and Toldrá, F., Elsevier, 2016, 1, p. 724-730Chapter in book (Refereed)
    Abstract [en]

    This article reviews briefly information regarding important food sources for folate, effects from storage and processing on folate content, and bioprocessing techniques that could provide foods with increased folate content. Thereafter, folate intake, absorption, metabolism, and bioavailability are also discussed. Finally, health effects associated with folate are presented briefly.

  • 43.
    Witthöft, Cornelia M.
    et al.
    Swedish Univ Agr Sci.
    Hefni, Mohammed E.
    Mansoura Univ, Egypt.
    Moazzami, Ali
    Swedish Univ Agr Sci.
    Folic acid supplement induces changes in 1-carbon metabolism of healthy women compared to food folate2015In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 67, p. 248-248Article in journal (Refereed)
  • 44. Öhrvik, Veronica E
    et al.
    Büttner, Barbara E
    Rychlik, Michael
    Lundin, Eva
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Folate bioavailability from breads and a meal assessed with a human stable-isotope area under the curve and ileostomy model.2010In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, no 3, p. 532-538Article in journal (Refereed)
    Abstract [en]

    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.

  • 45.
    Öhrvik, Veronica E
    et al.
    Sveriges lantbruksuniversitet, Uppsala.
    Olsson, Johan C
    Sveriges lantbruksuniversitet, Uppsala.
    Sundberg, Birgitta E
    Sveriges lantbruksuniversitet, Uppsala.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial.2009In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 89, no 4, p. 1053-1058Article in journal (Refereed)
    Abstract [en]

    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.

  • 46.
    Öhrvik, Veronica E
    et al.
    National Food Administration, Uppsala.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Human folate bioavailability2011In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 3, no 4, p. 475-490Article in journal (Refereed)
    Abstract [en]

    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.

  • 47.
    Öhrvik, Veronica
    et al.
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Can foods naturally high in folate improve folate status?: Results from an intervention trial2007In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 51, no suppl 1, p. 204-204, article id P306Article in journal (Refereed)
  • 48.
    Öhrvik, Veronica
    et al.
    Swedish University of Agricultural Sciences.
    Witthöft, Cornelia M.
    Swedish University of Agricultural Sciences.
    Orange juice is a good folate source in respect to folate content and stability during storage and simulated digestion2008In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 47, no 2, p. 92-98Article in journal (Refereed)
    Abstract [en]

    Background

    Estimated 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.

    Aims

    To (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).

    Methods

    Natural 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.

    Results

    5-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.

    Conclusion

    Orange 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.

  • 49. Öhrvik, Veronica
    et al.
    Öhrvik, Helena
    Tallkvist, Jonas
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Folates in bread: retention during bread-making and in vitro bioaccessibility2010In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 49, no 6, p. 365-372Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bread is an important folate source in several countries. However, bread-making was reported to cause losses of endogenous bread folates (approximately 40%) as well as added synthetic folic acid (approximately 30%). Furthermore, the bread matrix is suggested to inhibit absorption of folates.

    PURPOSE: To (1) estimate retention of both, endogenous folates and synthetic fortificants, during bread-making, (2) assess in vitro folate bioaccessibility from breads and a breakfast meal and (3) assess in vitro folate uptake.

    METHODS: Retention of folate forms was assessed by preparing fortified (folic acid and [6S]-5-CH(3)-H(4)folate) wholemeal breads and collect samples from dough, proofed dough and the bread. In vitro folate bioaccessibility was assessed using the TNO gastrointestinal model TIM. In vitro folate uptake was assessed using a novel Caco-2 cell/stable isotope model. Folate content in samples was measured using LCMS.

    RESULTS: Bread-making resulted in losses of 41% for endogenous folates and up to 25 and 65% for folic acid and [6S]-5-CH(3)-H(4)folate fortificant, respectively. 75% of endogenous bread folates and 94% of breakfast folates were bioaccessible as assessed by TIM. From [6S]-5-CH(3)-H(4)folate-fortified bread, relative folate uptake into Caco-2 cells was 71 +/- 11% (P < 0.05) when compared with a standard solution.

    CONCLUSION: Retention of folic acid fortificant during bread-making was substantially higher compared to retention of [6S]-5-CH(3)-H(4)folate fortificant. Data from the TIM and Caco-2 cell trials suggest an inhibiting effect of the tested bread matrices on in vitro bioaccessibility of folates, whereas folate bioaccessibility from a breakfast meal is almost complete.

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