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Folate bioavailability

Published online by Cambridge University Press:  07 March 2007

Helene McNulty  and
Kristina Pentieva
Helene McNulty*
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, UK
Kristina Pentieva
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, UK
*
*Corresponding author: Professor Helene McNulty, fax +44 28 7032 4965, email [email protected]
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Abstract

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The achievement of optimal folate status to prevent neural-tube defects, and possibly other diseases, is hindered by the well-recognised incomplete bioavailability of the natural folates found in foods compared with the synthetic vitamin, folic acid. Folate bioavailability from different foods is considered to be dependent on a number of factors, including the food matrix, the intestinal deconjugation of polyglutamyl folates, the instability of certain labile folates during digestion and the presence of certain dietary constituents that may enhance folate stability during digestion. There is conflicting evidence as to whether the extent of conjugation of polyglutamyl folate (in the absence of specific inhibitors of deconjugation in certain foods) is a limiting factor in folate bioavailability. Estimates of the extent of lower bioavailability of food folates compared with folic acid (relative bioavailability) show great variation, ranging anywhere between 10 and 98%, depending on the methodological approach used. The lack of accurate data on folate bioavailability from natural food sources is of particular concern in those countries in which there is no mandatory folic acid fortification, and therefore a greater reliance on natural food folates as a means to optimise status. Apart from the incomplete bioavailability of food folates, the poor stability of folates in foods (particularly green vegetables) under typical conditions of cooking can substantially reduce the amount of vitamin ingested and thereby be an additional factor limiting the ability of food folates to enhance folate status. A recent workshop convened by the Food Standards Agency concluded that gaining a better understanding of folate bioavailability in representative human diets is a high priority for future research.

Keywords

Food folateFolic acidFolate bioavailability methodologyFolate requirements
Type
Symposium on ‘Micronutrient interactions and public health’
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 4 , November 2004 , pp. 529 - 536
Copyright
Copyright © The Nutrition Society 2004

References

Afman, LA, Frans, JM & Trijbels, Blom HJ (2003) The H475Y polymorphism in the glutamate carboxypeptidase II gene increases plasma folate without affecting the risk for neural tube defects in humans. Journal of Nutrition 133, 75–77.CrossRefGoogle ScholarPubMed
Andersson, A & Oste, R (1992) Loss of ascorbic acid, folate and vitamin B12, and changes in oxygen content of UHT-milk, II. Results and discussion. Milchwissenschaft 47, 299–302.Google Scholar
Ashfield-Watt, PAL, Whiting, JM, Clark, ZE, Moat, SJ, Newcombe, RG, Burr, ML & McDowell, IFW (2003) A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine. European Journal of Clinical Nutrition 57, 316–323.CrossRefGoogle ScholarPubMed
Bailey, LB, Barton, LE Hillier, SE, Cerda JJ (1988) Bioavailability of mono and polyglutamyl folate in human subjects. Nutrition Reports International 38, 509–518.Google Scholar
Baker, H, Jaslow, SP & Frank, O (1978) Severe impairment of dietary folate utilization in the elderly. Journal of the American Geriatrics Society 26, 218–221.CrossRefGoogle ScholarPubMed
Bhandari, SD & Gregory, JF (1990) Inhibition by selected food components of human and porcine intestinal pteroylpolyglutamate hydrolase activity. American Journal of Clinical Nutrition 51, 87–94.CrossRefGoogle ScholarPubMed
Brouwer, IA, van, Dusseldorp, M, West, CE, Meyboom, S, Thomas, CMG, Duran, M, van het, Hof, KH, Eskes, TKAB, Hautvast, JGAJ, Steegers-Theunissen, RPM (1999) Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. Journal of Nutrition 129, 1135–1139.CrossRefGoogle Scholar
Brown, JP, Scott, JM, Foster, FG & Weir, DG (1973) Ingestion and absorption of naturally occurring pteroylmonoglutamates (folates) in man. Gastroenterology 64, 223–232.CrossRefGoogle ScholarPubMed
Butterworth, CE, Newman, AJ & Krumdieck, CL (1974) Tropical sprue: A consideration of possible etiologic mechanisms with emphasis on pteroylpolyglutamate metabolism. Transamerica Clinical Climatology Association 86, 11–22.Google Scholar
Castenmiller, JJM, van, de Poll, CJ, West, CE, Brouwer, IA, Thomas, CMG, van Dusseldorp M (2000) Bioavailability of folate from processed spinach in humans. Annals of Nutrition and Metabolism 44, 163–169.CrossRefGoogle ScholarPubMed
Choi, SW & Mason, JB (2000) Folate and carcinogenesis: An integrated scheme. Journal of Nutrition 130, 129–132.CrossRefGoogle ScholarPubMed
Colman, N, Green, R & Metz, J (1975) Prevention of folate deficiency by food fortification. II. Absorption of folic acid from fortified staple foods. American Journal of Clinical Nutrition 28, 459–464.CrossRefGoogle ScholarPubMed
Cuskelly, GJ, McNulty, H & Scott, JM (1996) Effect of increasing dietary folate on red-cell folate: Implications for prevention of neural tube defects. Lancet 347, 657–659.CrossRefGoogle ScholarPubMed
Czeizel, AE & Dudas, I (1992) Prevention of first occurrence of neural tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 327, 1832–1835.CrossRefGoogle ScholarPubMed
Dang, J, Arcot, J & Shrestha, A (2000) Folate retention in selected processed legumes. Food Chemistry 68, 295–298.CrossRefGoogle Scholar
De, Souza & SC, Eitenmiller RR (1986) Effects of processing and storage on the folate content of spinach and broccoli. Journal of Food Science 51, 626–628.Google Scholar
Devlin, AM, Ling, E, Peerson, JM, Fernando, S, Clarke, R, Smith, AD & Halsted, CH (2000) Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Human Molecular Genetics 9, 2837–2844.CrossRefGoogle ScholarPubMed
Fenech, M, Noakes, M, Clifton, P & Topping, D (1999) Aleurone flour is a rich source of bioavailable folate in humans. Journal of Nutrition 129, 1114–1119.CrossRefGoogle ScholarPubMed
Fletcher, RJ, Bell, IP & Lambert, JP (2004) Public health aspects of food fortification: a question of balance. Proceedings of the Nutrition Society 63, 605–614.CrossRefGoogle ScholarPubMed
Godwin, HA & Rosenberg, IH (1975) Comparative studies of the intestinal absorption of [3 H]pteroylmonoglutamate and [3 H]pteroylheptaglutamate in man. Gastroenterology 69, 364–373.CrossRefGoogle ScholarPubMed
Gregory, JF (1990) Improved synthesis of [3‘, 5’–2H2] folic acid: extent and specificity of deuterium labelling. Journal of Agricultural and Food Chemistry 38, 1073–1076.CrossRefGoogle Scholar
Gregory, JF (1995) The bioavailability of folate.In Folate: Nutritional and Clinical Perspectives, 195–235 [Bailey, LB, editors]. New York: Marcel Dekker.Google Scholar
Gregory, JF (2001) Case study: folate bioavailability. Journal of Nutrition 131, 1376S–1382S.CrossRefGoogle ScholarPubMed
Gregory, JF, Bhandari, SD, Bailey, LB, Toth, JP, Baumgartner, TG & Cerda, JJ (1992) Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects. American Journal of Clinical Nutrition 55, 1147–1153.CrossRefGoogle ScholarPubMed
Gregory, JF & Quinlivan, EP (2002) In vivo kinetics of folate metabolism. Annual Review of Nutrition 22, 199–220.CrossRefGoogle ScholarPubMed
Gregory, JF & Toth, JP (1990) Stable-isotopic methods for in vivo investigation of folate absorption and metabolism.In Folic Acid Metabolism in Health and Disease, 151–169 [Picciano, MF,Stokstad, ELR and Gregory, JF, editors]. New York: Wiley-Liss Inc.Google Scholar
Halsted, CH (1990) Intestinal absorption of dietary folates.In Folic Acid Metabolism in Health and Disease, 23–45 [Picciano, MF,Stokstad, ELR and Gregory, JF, editors]. New York: Wiley-Liss Inc.Google Scholar
Hannon-Fletcher, MP, Armstrong, NC, Scott, JM, Pentieva, K, Bradbury, I, Ward, M, Strain, JJ, Dunn, AA, Molloy, AM, Scullion, MA & McNulty, H (2004) Determination of the bioavailability of food folates in a controlled intervention study American Journal of Clinical Nutrition.Google Scholar
Hurdle, ADF, Barton, D & Searles, IH (1968) A method for measuring folate in foods and its application to a hospital diet. American Journal of Clinical Nutrition 21, 1202–1207.CrossRefGoogle ScholarPubMed
Institute of MedicineInstitute of Medicine (1998) Dietary Reference Intake; Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press..Google Scholar
Keagy, PM, Shane, B & Oace, SM (1988) Folate bioavailability in humans: effect of wheat bran and beans. American Journal of Clinical Nutrition 47, 80–88.CrossRefGoogle ScholarPubMed
Konings, EJM, Troost, FJ, Castenmiller, JJM, Roomans, HHS, van, den, Brandt, PA & Saris, WHM (2002) Intestinal absorption of different types of folate in healthy subjects with an ileostomy. British Journal of Nutrition 88, 235–242.CrossRefGoogle ScholarPubMed
Lamers, Y, Prinz-Langenohl, R, Moser, R & Pietrzik, K (2004) Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. American Journal of Clinical Nutrition 79, 473–478.CrossRefGoogle ScholarPubMed
Leichter, J, Switzer, VP & Landymore, AF (1978) Effect of cooking on folate content of vegetables. Nutrition Reports International 18, 475–479.Google Scholar
Lievers, KJA, Kluijtmans, LAJ, Boers, GHJ, Verhoef, P, den, Heijer, M, Trijbels, FJM, Blom HJ (2002) Influence of glutamate carboxypeptidase II (GCPII) polymorphism (1561C→T) on plasma homocysteine, folate and vitamin B 12 levels and its relationship to cardiovascular disease risk. Atherosclerosis 164, 269–273.CrossRefGoogle ScholarPubMed
McKillop, D, Pentieva, K, Daly, D, McPartlin, JM, Hughes, J, Strain, JJ, Scott, JM & McNulty, H (2002) The effect of different cooking methods on folate retention in various foods which are amongst the major contributors to folate intake in the UK diet. British Journal of Nutrition 88, 681–688.CrossRefGoogle ScholarPubMed
Maunder, P, Finglas, PM, Mallet, AI, Mellon, FA, Razzaque, MA, Ridge, B, Vahteristo, L & Witthoft, C (1999) The synthesis of folic acid, multiple labelled with stable isotopes, for bioavailability studies in human nutrition. Journal of the Chemical Society Perkin Transaction 1, 1311–1323.CrossRefGoogle Scholar
Medical, Research, Council, Vitamin, Study, Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338, 131–137.Google Scholar
Melse-Boonstra, A, de, Bree, A, Verhoef, P, Bjorke-Monsen, AL, Verschuren WMM (2002) Dietary monoglutamate and polyglutamate folate are both associated with plasma folate concentrations in Dutch men and women aged 20–65 y. Journal of Nutrition 132, 1307–1312.CrossRefGoogle Scholar
Melse-Boonstra, A, West, CE, Katan, MB, Kok, FJ & Verhoef, P (2004) Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults. American Journal of Clinical Nutrition 79, 424–429.CrossRefGoogle ScholarPubMed
Murphy, M, Keating, M, Boyle, P, Weir, DG & Scott, JM (1976) The elucidation of the mechanism of folate catabolism in the rat. Biochemical and Biophysical Research Communications 71, 1017–1024.CrossRefGoogle ScholarPubMed
Pentieva, K, Kidd, JA, McKillop, DJ, Strain, JJ, Scott, JM & McNulty, H (2002) Folate analysis of composite meals. Proceedings of the Nutrition Society 61 92A.Google Scholar
Pentieva, K, McNulty, H, Reichert, R, Ward, M, Strain, JJ, McKillop, D, McPartlin, JM, Connolly, E, Molloy, A, Krämer, K & Scott, JM (2004) The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. Journal of Nutrition 134, 580–585.CrossRefGoogle ScholarPubMed
Pfeiffer, CM, Rogers, LM, Bailey, LB & Gregory, JF (1997) Absorption of folate from fortified cereal-grain products and of supplemental folate consumed with or without food determined by using a dual-label stable-isotope protocol. American Journal of Clinical Nutrition 66, 1388–1397.CrossRefGoogle ScholarPubMed
Perry, J & Chanarin, I (1970) Intestinal absorption of reduced folate compounds in man. British Journal of Haematology 18, 329–339.CrossRefGoogle ScholarPubMed
Pietrzik, K, Hages, M & Remer, T (1990) Methodological aspects in vitamin bioavailability testing. Journal of Micronutrient Analysis 7, 207–222.Google Scholar
Pietrzik, K & Remer, T (1989) Zur Bioverfugbarkeitsprufung von Mikronahrstoffen (Bioavailability study of micronutrients). Zeitschrift fur Ernahrungawissenschaft 28, 130–141.CrossRefGoogle ScholarPubMed
Prinz-Langenohl, R, Bronstrup, A, Thorand, B, Hages, M & Pietrzik, K (1999) Availability of food folate in humans. Journal of Nutrition 129, 913–916.CrossRefGoogle ScholarPubMed
Reisenauer, AM & Halsted, CH (1987) Human folate requirements. Journal of Nutrition 117, 600–602.CrossRefGoogle ScholarPubMed
Riddell, LJ, Chisholm, A, Williams, S & Mann, JI (2000) Dietary strategies for lowering homocysteine concentrations. American Journal of Clinical Nutrition 71, 1448–1454.CrossRefGoogle ScholarPubMed
Rosenberg, IH & Godwin, HA (1971) Inhibition of intestinal γ-glutamyl carboxypeptidase by yeast nucleic acid: an explanation of variability in utilisation of dietary polyglutamyl folate. Journal of Clinical Investigation 50, 78a.Google Scholar
Sanderson, P, McNulty, H, Mastroiacovo, P, McDowell, IFW, Melse-Boonstra, A, Finglas, PM, Gregory, JF III (2003) Folate bioavailability: UK Food Standards Agency workshop report. British Journal of Nutrition 90, 473–479.CrossRefGoogle ScholarPubMed
Sauberlich, HE, Kretsch, MJ, Skala, JH, Johnson, HL & Taylor, RC (1987) Folate requirement and metabolism in nonpregnant women. American Journal of Clinical Nutrition 46, 1016–1028.CrossRefGoogle ScholarPubMed
Seshadri, S, Beiser, A, Selhub, J, Jacques, PF, Rosenberg, IH, D'Agostino, RB, Wison, PWF & Wolf, PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. New England Journal of Medicine 346, 476–483.CrossRefGoogle ScholarPubMed
Seyom, E & Selhub, J (1998) Properties of food folates determined by stability and susceptibility to intestinal pteroylpolyglutamate hydrolase action. Journal of Nutrition 128, 1956–1960.CrossRefGoogle Scholar
Smith, AM, Picciano, MF & Deering, RH (1985) Folate intake and blood concentrations of term infants. American Journal of Clinical Nutrition 41, 590–598.CrossRefGoogle ScholarPubMed
Strain, JJ, Dowey, L, Ward, M, Pentieva, K & McNulty, H (2004) B-vitamins, homocysteine metabolism and CVD. Proceedings of the Nutrition Society 63, 597–603.CrossRefGoogle ScholarPubMed
Tamura, T, Mizuno, Y, Johnston, KE & Jacob, RA (1997) Food folate assay with protease, α-amylase and folate conjugase treatments. Journal of Agricultural and Food Chemistry 45, 135–139.CrossRefGoogle Scholar
Tamura, T, Shin, YS, Buehring, KU & Stokstad, ELR (1976) The availability of folate in man: Effect of orange juice supplement on intestinal conjugase. British Journal of Haematology 32, 123–133.CrossRefGoogle ScholarPubMed
Tamura, T & Stokstad, ELR (1973) The availability of food folate in man. British Journal of Haematology 25, 513–532.CrossRefGoogle ScholarPubMed
van, het, Hof, KH, Tijburg, LBM, Pietrzik, K & Weststrate, JA (1999) Influence of feeding different vegetables on plasma levels of carotenoids, folate and vitamin C. Effect of disruption of the vegetable matrix. British Journal of Nutrition 82, 203–212.Google Scholar
Vargas-Martinez, C, Ordovas, JM, Wilson, PW & Selhub, J (2002) The glutamate carboxypeptidase gene II (CT) polymorphism does not affect folate status in the Framingham Offspring cohort. Journal of Nutrition 132, 1176–1179.CrossRefGoogle Scholar
Venn, BJ, Green, TJ, Moser, R, McKenzie, JE, Skeaff, CM & Mann, J (2002) Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. Journal of Nutrition 132, 3353–3355.CrossRefGoogle ScholarPubMed
Venn, BJ, Green, TJ, Moser, R & Mann, JI (2003) Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. American Journal of Clinical Nutrition 77, 658–662.CrossRefGoogle ScholarPubMed
Wald, DS, Law, M & Morris, JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. British Medical Journal 325, 1–7.CrossRefGoogle ScholarPubMed
Wei, MM, Bailey, LB, Toth, JP & Gregory, JF (1996) Bioavailability for humans of deuterium-labeled monoglutamyl and polyglutamyl folates is affected by selected foods. Journal of Nutrition 126, 3100–3108.CrossRefGoogle ScholarPubMed
Wei, MM & Gregory, JF (1998) Organic acids in selected foods inhibit intestinal brush border pteroylpolyglutamate hydrolase in vitro: potential mechanism affecting the bioavailability of dietary polyglutamyl folate. Journal of Agricultural and Food Chemistry 46, 211–219.CrossRefGoogle ScholarPubMed
Wright, AJA, Finglas, PM, Dainty, JR, Hart, DJ, Wolfe, CA, Southon, S & Gregory, JF (2003) Single oral doses of 13C forms of pteroylmonoglutamic acid and 5-formyltetrahydrofolic acid elicit differences in short-term kinetics of labelled and unlabelled folates in plasma: potential problems in interpretation of folate bioavailability studies. British Journal of Nutrition 90, 363–371.CrossRefGoogle Scholar