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  • 51.
    Witthöft, Cornelia M
    et al.
    Sveriges Lantbruksuniversitet.
    Forssén, Karin
    Sveriges Lantbruksuniversitet.
    Johannesson, Lena
    Sveriges Lantbruksuniversitet.
    Jägerstad, Margareta
    Sveriges Lantbruksuniversitet.
    Folates - Food sources, analyses, retention and bioavailability1999Ingår i: Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, EISSN 1651-2359, Vol. 43, nr 4, s. 138-146Artikel i tidskrift (Refereegranskat)
  • 52.
    Witthöft, Cornelia M.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Hefni, Mohammed E.
    Mansoura University, Egypt.
    Folic acid and Folates: Physiology and Health Effects2016Ingår i: The Encyclopedia of Food and Health / [ed] Caballero, B., Finglas, P., and Toldrá, F., Elsevier, 2016, 1, s. 724-730Kapitel i bok, del av antologi (Refereegranskat)
    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.

  • 53.
    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 folate2015Ingår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 67, s. 248-248Artikel i tidskrift (Refereegranskat)
  • 54.
    Witthöft, Cornelia M
    et al.
    Sveriges Lantbrunksuniversitet.
    Jägerstad, Margaretha
    Sveriges Lantbruksuniversitet.
    Bitsch, I
    Justus Liebig University .
    Folate content and bioavailability in food using HPLC-methods and a human model1999Ingår i: VITAMINE UND ZUSATZSTOFFE IN DER ERNAHRUNG VON MENSCH UND TIER, s. 109-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Methods for the extraction, stabilization, deconjugation, purification and subsequent HPLC determination of folates from biological material were presented. All methods were externally validated by participation in European intercomparison studies. They were successfully applied to determine folate concentrations in food and human plasma for biokinetical purposes.

  • 55.
    Witthöft, Cornelia M
    et al.
    Sveriges Lantbruksuniversitet.
    Strålsjö, Lena
    Sveriges Lantbruksuniversitet.
    Berglund, Gerd
    Umeå Universitet.
    Lundin, Eva
    Umeå Universitet.
    A human model to determine folate bioavailability from food: A pilot study for evaluation2003Ingår i: Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, E-ISSN 1651-2359, Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, EISSN 1651-2359, Vol. 47, nr 1, s. 6-18, artikel-id https://doi.org/10.3402/fnr.v47i1.1465Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Knowledge about folate bioavailability from food is essential for the estimation of dietary requirements. Yet, there is a lack of data obtained from validated human studies performed with physiological folate doses. Objective: In this pilot study, a new model for the determination of folate absorption is developed and validated. Design: Under strictly standardized procedures, two healthy ileostomy volunteers consumed single portions of test foods or an oral dose of a pharmaceutical folate preparation of the natural folate diastereomer (6S)-5- methyltetrahydrofolate. Relative folate absorption from oral doses versus an intramuscular injection of the same pharmaceutical preparation was determined using postdose plasma folate concentration curves. Nonabsorbed folate was estimated by postdose folate excretion into stomal effluent. Results: Estimated by plasma areas under the curve, relative folate absorption ranged from 47 to 67% for oral doses from the te st foods strawberries and broccoli and the pharmaceutical (6S)-5-methyltetrahydrofolate preparation. During 10 h postdose, 19-44% of the dietary folate was excreted with the stomal effluent. Varying gut passage times were observed for different food matrices by determining ileostomal folate excretion in 2 h intervals. Around 90% of the folate from the oral doses was recovered in the collected body fluids, plasma and stomal effluent, by 10 h postdose, independent of the size of the administered folate doses of 200 or 400 mg (0.4 or 0.9 mmol). Conclusion: The results imply that this model provides a suitable tool to estimate folate bioavailability from foods.

  • 56. 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.2010Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 3, s. 532-538Artikel i tidskrift (Refereegranskat)
    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.

  • 57.
    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.2009Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 89, nr 4, s. 1053-1058Artikel i tidskrift (Refereegranskat)
    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.

  • 58.
    Öhrvik, Veronica E
    et al.
    National Food Administration, Uppsala.
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Human folate bioavailability2011Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 3, nr 4, s. 475-490Artikel i tidskrift (Refereegranskat)
    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.

  • 59.
    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 trial2007Ingår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 51, nr suppl 1, s. 204-204, artikel-id P306Artikel i tidskrift (Refereegranskat)
  • 60.
    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 digestion2008Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 47, nr 2, s. 92-98Artikel i tidskrift (Refereegranskat)
    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.

  • 61. Öhrvik, Veronica
    et al.
    Öhrvik, Helena
    Tallkvist, Jonas
    Witthöft, Cornelia M.
    Sveriges lantbruksuniversitet, Uppsala.
    Folates in bread: retention during bread-making and in vitro bioaccessibility2010Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 49, nr 6, s. 365-372Artikel i tidskrift (Refereegranskat)
    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.

  • 62.
    Östman, Johnny R.
    et al.
    Swedish University of Agricultural Sciences, Sweden.
    Müllner, Elisabeth
    Swedish University of Agricultural Sciences, Sweden.
    Eriksson, Jan
    Swedish University of Agricultural Sciences, Sweden.
    Kristinsson, Hjalti
    Uppsala university, Sweden.
    Gustafsson, Jan
    Uppsala university, Sweden.
    Witthöft, Cornelia M.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Bergsten, Peter
    Uppsala university, Sweden.
    Moazzami, Ali A.
    Swedish University of Agricultural Sciences, Sweden.
    Glucose Appearance Rate Rather than the Blood Glucose Concentrations Explains Differences in Postprandial Insulin Responses between Wholemeal Rye and Refined Wheat Breads—Results from A Cross-Over Meal Study2019Ingår i: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 63, nr 7, s. 1-9, artikel-id 1800959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Scope: Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy. Methods and results: Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6- 2 H 2 ]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0‒90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0‒90 min AUC. Conclusion: Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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