Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-22T23:16:25.690Z Has data issue: false hasContentIssue false
  • English
  • Français

Bioavailability and bioefficacy of folate and folic acid in man

Published online by Cambridge University Press:  14 December 2007

Ingeborg A. Brouwer ,
Maryke van Dusseldorp ,
Clive E. West  and
Régine P.M. Steegers-Theunissen
Ingeborg A. Brouwer*
Affiliation:
Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands
Maryke van Dusseldorp
Affiliation:
Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands
Clive E. West
Affiliation:
Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands Department of Gastroenterology, University Hospital Nijmegen St Radboud, The Netherlands
Régine P.M. Steegers-Theunissen
Affiliation:
Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands Department of Epidemiology, University Hospital Nijmegen St Radboud, The Netherlands
*
*Corresponding author: Dr Ingeborg A. Brouwer, present address Wageningen Centre for Food Sciences, PO Box 8129, 6700 EV Wageningen, The Netherlands, fax +33 317 483342, email: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Folic acid is important because supplementation around the time of conception has been proven to lower the risk of having offspring with a neural-tube defect. Furthermore, both dietary folate and folic acid decrease plasma total homocysteine concentrations. Elevated plasma homocysteine concentrations are considered to be an independent risk factor for cardiovascular disease. The aim of the present review is to give an overview of factors influencing bioavailability and bioefficacy (the proportion of ingested nutrient converted to its active form) of food folate and folic acid, and to discuss the functional bioefficacy of folate and folic acid in decreasing plasma homocysteine concentrations. We use the mnemonic SLAMENGHI to group factors influencing bioavailability and bioefficacy: Species of folate; Linkage at molecular level; Amount of folate and folic acid consumed; Matrix; Effect modifiers; Nutrient status; Genetic factors; Host-related factors; mathematical Interactions between the various factors. Bioefficacy of folate from some foods is 50 % that of folic acid. This factor is most probably explained by the matrix factors, encapsulation and binding. However, often such effects cannot be distinguished from factors such as species, chain length of folate in food, effect modifiers and the amount of folate consumed in a meal. Folic acid provided as a supplement is well absorbed. However, the homocysteine-lowering capacity of doses of folic acid >500 μg is limited. It is unclear whether unmetabolised folic acid poses health risks. This factor is of importance, because food fortification is now implemented in many countries and folic acid supplements are freely available. In particular circumstances host-related factors, such as gastrointestinal illness and pH of the jejunum, can influence bioavailability. Genetic factors also deserve attention for future research, because polymorphisms may influence folate bioavailability.

Keywords

FolateFolic acidBioavailabilityBioefficacyHomocysteine
Type
Research Article
Information
Nutrition Research Reviews , Volume 14 , Issue 2 , December 2001 , pp. 267 - 294
Copyright
Copyright © CABI Publishing 2001

References

Appel, LJ, Miller, ER III, Jee, SH, Stolzenberg-Solomon, R, Lin, P-H, Erlinger, T, Nadeau, MR & Selhub, J (2000) Effect of dietary patterns on serum homocysteine. Results of a randomized, controlled feeding study. Circulation 102, 852–857.Google Scholar
Babu, S & Lakshmaiah, N (1987) Availability of food folate by liver folate repletion in rats. Nutrition Reports International 35, 831–836.Google Scholar
Babu, S & Srikantia, SG (1976) Availability of folates from some foods. American Journal of Clinical Nutrition 29, 376–379.Google Scholar
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
Bailey, LB, Cerda, JJ, Bloch, BS, Busby, MJ, Vargas, L, Chandler, CJ & Halsted, CH (1984) Effect of age on poly- and monoglutamyl folacin absorption in human subjects. Journal of Nutrition 114, 1770–1776.Google Scholar
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.Google Scholar
Bhandari, SD & Gregory, JF (1992) Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats. Journal of Nutrition 122, 1847–1854.Google Scholar
Bonnette, RE, Caudill, MA, Boddie, AM, Hutson, AD, Kauwell, GPA & Bailey, LB (1998) Plasma homocyst(e)ine concentrations in pregnant and nonpregnant women with controlled folate intake. Obstetrics and Gynecology 92, 167–170.Google ScholarPubMed
Boushey, CJ, Beresford, SA, Omenn, GS & Motulsky, AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. Journal of the American Medical Association 274, 1049–1057.Google Scholar
Bower, C, Stanley, FJ, Croft, M, de Klerk, N, Davis, RE & Nicol, DJ (1993) Absorption of pteroylpolyglutamates in mothers of infants with neural-tube defects. British Journal of Nutrition 69, 827–834.CrossRefGoogle ScholarPubMed
Brouwer, IA, van Dusseldorp, M, Thomas, CMG, Duran, M, Hautvast, JGAJ, Eskes, TKAB & Steegers Theunissen, RPM (1999) Low-dose folic acid supplementation decreases plasma homocysteine: a randomized trial. American Journal of Clinical Nutrition 69, 99–104.Google Scholar
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 study. Journal of Nutrition 129, 1135–1139.Google Scholar
Brown, JP, Scott, JM, Foster, FG & Weir, DG (1973) Ingestion and absorption of naturally occurring pteroylmonoglutamates (folates) in man. Gastroenterology 64, 223–232.Google Scholar
Brussaard, JH, van der Berg, H, Brants, HAM, van Loon, CJAM & Löwik, MRH (1995) Folate Intake and Status among Adults in The Netherlands (Dutch Nutrition Surveillance System). Descriptive Statistics. Zeist, The Netherlands: TNO Nutrition.Google Scholar
Cassady, IA, Budge, MM, Healy, MJ & Nixon, PF (1980) An inverse relationship of rat liver folate polyglutamate chain length to nutritional folate sufficiency. Biochimica et Biophysica Acta 633, 258–268.Google Scholar
Castenmiller, JJM & West, CE (1998) Bioavailability and conversion of carotenoids. Annual Review of Nutrition 18, 19–38.Google Scholar
Caudill, MA, Cruz, AC, Gregory, JF, Hutson, AD & Bailey, LB (1997) Folate status response to controlled folate intake in pregnant women. Journal of Nutrition 127, 2363–2370.Google Scholar
Caudill, MA, Gregory, JF, Hutson, AD & Bailey, LB (1998) Folate catabolism in pregnant and nonpregnant women with controlled folate intakes. Journal of Nutrition 128, 204–208.Google Scholar
Chandler, CJ, Wang, XL & Halsted, CH (1986) Pteroylpolyglutamate hydrolase from human jejunal brush borders; purification and characterization. Journal of Biological Chemistry 261, 928–933.Google Scholar
Chiao, JH, Roy, K, Tolner, B, Yang, C-H & Sirotnak, FM (1997) RFC-1 gene expression regulates folate absorption in mouse small intestine. Journal of Biological Chemistry 272, 11165–11170.Google Scholar
Cichowicz, DJ & Shane, B (1987) Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme. Biochemistry 26, 504–512.Google Scholar
Cichowicz, DJ & Shane, B (1987) Mammalian folylpoly-gamma-glutamate synthetase. 2. Substrate specificity and kinetic properties. Biochemistry 26, 513–521.Google Scholar
Colman, N (1982) Addition of folic acid to staple foods as a selective nutrition intervention strategy. Nutrition Reviews 40, 225–233.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.Google Scholar
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.Google Scholar
Czeizel, AE & Dudás, I (1992) Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 327, 1832–1835.Google Scholar
Davis, BA, Bailey, LB, Gregory, JF, Toth, JP, Dean, J & Stevenson, RE (1995) Folic acid absorption in women with a history of pregnancy with neural tube defect. American Journal of Clinical Nutrition 62, 782–784.Google Scholar
de Pee, S & West, CE (1996) ietary carotenoids and their role in combating vitamin A deficiency: a review of the literature. European Journal of Clinical Nutrition 50, Suppl 3, S38–S53.Google Scholar
Eichner, ER & Hillman, RS (1973) Effect of alcohol on serum folate level. Journal of Clinical Investigation 52, 584–591.Google Scholar
Godwin, HA & Rosenberg, IH (1975) Comparative studies of the intestinal absorption of [3H ]pteroylmonoglutamate and [3H ]pteroylheptaglutamate in man. Gastroenterology 69, 364–373.Google Scholar
Goyette, P, Sumner, JS, Milos, R, Duncan, AM, Rosenblatt, DS, Matthews, RG & Rozen, R (1994) Human methylene-tetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nature Genetics 7, 195–200, 551.CrossRefGoogle ScholarPubMed
Graham, IM, Daly, LE & Refsum, HM (1997) Plasma homocysteine as a risk factor for cardiovascular disease. Journal of the American Medical Association 277, 1775–1781.Google Scholar
Gregory, JF, Bhandari, SD, Bailey, LB, Toth, JP, Baumgartner, TG & Cerda, JJ (1991) Relative bioavailability of deuterium-labeled monoglutamyl and hexaglutamyl folates in human subjects. American Journal of Clinical Nutrition 53, 736–740.Google Scholar
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.Google Scholar
Halsted, CH (1979) The intestinal absorption of folates. American Journal of Clinical Nutrition 32, 846–855.CrossRefGoogle ScholarPubMed
Halsted, CH (1990) Intestinal absorption of dietary folates. In Folic Acid Metabolism in Health and Disease, 1st ed., pp. 23–45 [Picciano, MF, Stokstad, ELR and Gregory, JF III editors]. New York: Wiley-Liss.Google Scholar
Halsted, CH (1995) Alcohol and folate interactions: Clinical implications. In Folate in Health and Disease, pp. 313–327 [Bailey, LB editor]. New York: Marcel Dekker.Google Scholar
Halsted, CH, Baugh, CM & Butterworth, CE (1975) Jejunal perfusion of simple and conjugated folates in man. Gastroenterology 68, 261–269.Google Scholar
Halsted, CH, Reisenauer, AM, Shane, B & Tamura, T (1978) Availability of monoglutamyl and polyglutamyl folates in normal subjects and in patients with coeliac sprue. Gut 19, 886–891.Google Scholar
Halsted, CH, Robles, EA & Mezey, E (1971) Decreased jejunal uptake of labeled folic acid (3H-PGA) in alcoholic patients: roles of alcohol and malnutrition. New England Journal of Medicine 285, 701–706.Google Scholar
Herbert, V & Zalusky, R (1962) Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. Journal of Clinical Investigation 41, 1263–1276.Google Scholar
Homocysteine Lowering Trialists' Collaboration (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. British Medical Journal 316, 894–898.Google Scholar
Jacob, RA, Pianalto, FS, Henning, SM, Zhang, JZ & Swendseid, ME (1995) In vivo methylation capacity is not impaired in healthy men during short-term dietary folate and methyl group restriction. Journal of Nutrition 125, 1495–1502.Google Scholar
Jacques, PF, Bostom, AG, Williams, RR, Ellison, RC, Eckfeldt, JH, Rosenberg, IH, Selhub, J & Rozen, R (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7–9.Google Scholar
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PWF & Rosenberg, IH (1999) The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New England Journal of Medicine 340, 1449–1454.CrossRefGoogle ScholarPubMed
Kang, S-S, Zhou, J, Wong, PWK, Kowalysin, J & Strokosch, G (1988) Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. American Journal of Human Genetics 43, 414–421.Google ScholarPubMed
Kauwell, GPA, Bailey, LB, Gregory, JF, Bowling, DW & Cousins, RJ (1995) Zinc status is not adversely affected by folic acid supplementation and zinc does not impair folate utilization in human subjects. Journal of Nutrition 125, 66–72.Google Scholar
Keagy, PM, Shane, B & Oace, SM (1988) Folate bioavailability in humans: effects of wheat bran and beans. American Journal of Clinical Nutrition 47, 80–88.Google Scholar
Kelly, P, McPartlin, JM, Goggins, M, Weir, DG & Scott, JM (1997) Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. American Journal of Clinical Nutrition 65, 1790–1795.Google Scholar
Kownacki Brown, PA, Wang, C, Bailey, LB, Toth, JP & Gregory, JF (1993) Urinary excretion of deuterium-labeled folate and the metabolite p-aminobenzoylglutamate in humans. Journal of Nutrition 123, 1101–1108.Google Scholar
Lawrence, JM, Petiti, DB, Watkins, M & Umekubo, MA (1999) Trends in serum folate after food fortification. Lancet 354, 915–916.Google Scholar
Lowe, KE, Osborne, CB, Lin, BF, Kim, JS, Hsu, JC & Shane, B (1993) Regulation of folate and one-carbon metabolism in mammalian cells. II. Effect of folylpoly-gamma-glutamate synthetase substrate specificity and level on folate metabolism and folylpoly-gamma-glutamate specificity of metabolic cycles of one-carbon metabolism. Journal of Biological Chemistry 268, 21665–21673.Google Scholar
McPartlin, JM, Halligan, A, Scott, JM, Darling, MD & Weir, DG (1993) Accelerated folate breakdown in pregnancy. Lancet 341, 148–149.Google Scholar
Malinow, MR, Duell, PB, Hess, DL, Anderson, PH, Kruger, WD, Phillipson, BE, Gluckman, RA, Block, PC & Upson, BM (1998) Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. New England Journal of Medicine 338, 1009–1015.Google Scholar
Margo, G, Barker, M, Fernandez-Costa, F, Colman, N, Green, R & Metz, J (1975) Prevention of folate deficiency by food fortification. VII. The use of bread as a vehicle for folate supplementation. American Journal of Clinical Nutrition 28, 761–763.Google Scholar
Mason, JB (1990)Intestinal transport of monoglutamyl folates in mammalian systems. In Folic Acid Metabolism in Health and Disease, 1st ed, pp. 47–64 [Picciano, MF, Stokstad, ELR and Gregory, JF III editors ]. New York: Wiley-Liss.Google 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
Naughton, CA, Chandler, CJ, Duplantier, RB & Halsted, CH (1989) Folate absorption in alcoholic pigs: in vitro hydrolysis and transport at the intestinal brush border membrane. American Journal of Clinical Nutrition 50, 1436–1441.Google Scholar
Neuhouser, ML, Beresford, SAA, Hickok, DE & Monsen, ER (1998) Absorption of dietary folate and supplemental folate in women with prior pregnancies with neural tube defects and controls. Journal of the American College of Nutrition 6, 625–630.Google Scholar
Perry, J & Chanarin, I (1970) Intestinal absorption of reduced folate compounds in man. British Journal of Haematology 18, 329–339.Google Scholar
Perry, J & Chanarin, I (1973) Formylation of folates as a step in physiological folate absorption. British Medical Journal ii, 58–59.Google Scholar
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.Google Scholar
Pietrzik, K & Remer, T (1989) Zur Bioverfugbarkeitsprufung von Mikronahrstoffen (Bioavailability study of micro-nutrients). Zeitschrift für Ernahrungswissenschaft 28, 130–141.Google Scholar
Reisenauer, A & Halsted, C (1987) Human folate requirements. Journal of Nutrition 117, 600–602.Google Scholar
Reisenauer, AM, Buffington, CAT, Villanueva, JA & Halsted, CH (1989) Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. American Journal of Clinical Nutrition 50, 1429–1435.Google Scholar
Reisenauer, AM, Krumdieck, CL & Halsted, CH (1977) Folate conjugase: two separate activities in human jejunum. Science 198, 196–197.CrossRefGoogle ScholarPubMed
Retief, FP (1969) Urinary folate excretion after ingestion of pteroylmonoglutamic acid and food folate. American Journal of Clinical Nutrition 22, 352–355.CrossRefGoogle ScholarPubMed
Richardson, RE, Healy, MJ & Nixon, PF (1979) Folates of rat tissue. Bioassay of tissue folylpolyglutamates and a relationship of liver folylpolyglutamates to nutritional folate sufficiency. Biochimica et Biophysica Acta 585, 128–133.CrossRefGoogle Scholar
Riddell, LJ, Chisholm, A, Williams, S & Mann, JI (2000) Dietary strategies for lowering homocysteine concentrations. American Journal of Clinical Nutrition 71, 1448–1454.Google Scholar
Rogers, LM, Pfeiffer, CM, Bailey, LB & Gregory, JF (1997) A dual-label stable-isotopic protocol is suitable for determination of folate bioavailability in humans: evaluation of urinary excretion and plasma folate kinetics of intravenous and oral doses of [13C5 ] and [2H2 ]folic acid. Journal of Nutrition 127, 2321–2327.Google Scholar
Rosenberg, IH & Godwin, HA (1971) The digestion and absorption of dietary folate. Gastroenterology 60, 445–463.Google Scholar
Rowland, M & Tozer, TN (1989) Clinical Pharmacokinetics: Concepts and Applications. Philadelphia, PA: Lea & Febiger.Google Scholar
Russell, RM, Rosenberg, IH, Wilson, PD, Iber, FL, Oaks, EB, Giovetti, AC, Otradovec, CL, Karwoski, PA & Press, AW (1983) Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion. American Journal of Clinical Nutrition 38, 64–70.Google Scholar
Sauberlich, HE, Kretsch, MJ, Skala, JH., Johnson, HL & Taylor, PC (1987) Folate requirement and metabolism in nonpregnant women. American Journal of Clinical Nutrition 46, 1016–1028.Google Scholar
Savage, DG & Lindenbaum, JL (1995) Folate-cobalamin interactions. In Folate in Health and Disease, pp. 237–285 [Bailey, LB editor]. New York, Marcel Dekker.Google Scholar
Schorah, CJ, Devitt, H, Lucock, M & Dowell, AC (1998) The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. European Journal of Clinical Nutrition 52, 407–411.Google Scholar
Selhub, J, Brin, H & Grossowicz, N (1973) Uptake and reduction of radioactive folate by everted sacs of rat small intestine. European Journal of Biochemistry 33, 433–438.Google Scholar
Selhub, J, Dhar, GJ & Rosenberg, IH (1983) Gastrointestinal absorption of folates and antifolates. Pharmacology and Therapeutics 20, 397–418.Google Scholar
Shane, B (1995) Folate chemistry and metabolism. In Folate in Health and Disease, pp. 1–22 [Bailey, LB editor]. New York: Marcel Dekker.Google Scholar
Strum, WB (1979) Enzymatic reduction and methylation of folate following pH-dependent carrier-mediated transport in rat jejunum. Biochimica et Biophysica Acta 554, 249–257.Google Scholar
Tamura, T (1995) Nutrient interaction of folate and zinc. In Folate in Health and Disease, pp. 287–312 [Bailey, LB editor]. New York: Marcel Dekker.Google Scholar
Tamura, T, Shane, B, Baer, MT, King, JC, Margen, S & Stokstad, ELR (1978) Absorption of mono- and polyglutamyl folates in zinc-depleted man. American Journal of Clinical Nutrition 31, 1984–1987.Google Scholar
Tamura, T & Stokstad, ELR (1973) The availability of food folate in man. British Journal of Haematology 25, 513–532.Google Scholar
Tolner, B, Roy, K & Sirotnak, FM (1998) Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promotors and alternatively spliced transcrips with 5′ end heterogeneity. Gene 211, 331–341.Google Scholar
Truswell, AS & Kounnavong, S (1997) Quantitative responses of serum folate to increasing intakes of folic acid in healthy women. European Journal of Clinical Nutrition 51, 839–845.Google Scholar
US Department of Health and Human Services, Food and Drug Administration (1996) Food standards: amendment of the standards of identity for enriched grain products to require addition of folic acid. Federal Register 61, 8781–8807.Google Scholar
Van Lieshout, M, West, CE, Muhilal, , Permaesih, D, Wang, Y, Xu, X, Van Breemen, RB, Creemers, AFL, Verhoeven, MA & Lugtenburg, J (2001) Bioefficacy of beta-carotene dissolved in oil studied in children in Indonesia. American Journal of Clinical Nutrition 73, 949–958.Google Scholar
Varela-Moreiras, G & Selhub, J (1992) Long-term folate deficiency alters folate content and distribution differentially in rat tissues. Journal of Nutrition 122, 986–991.Google Scholar
Wagner, C (1995) Biochemical role of folate in cellular metabolism. In Folate in Health and Disease, pp. 23–42 [Bailey, LB editor]. New York: Marcel Dekker.Google Scholar
Ward, GJ & Nixon, PF (1990) Modulation of pteroylpolyglutamate concentration and length in response to altered folate nutrition in a comprehensive range of rat tissues. Journal of Nutrition 120, 476–484.Google Scholar
Ward, M, McNulty, H, McPartlin, J, Strain, JJ, Weir, DG & Scott, JM (1997) Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. Quarterly Journal of Medicine 90, 519–524.CrossRefGoogle ScholarPubMed
Wei, MM, Bailey, LB, Toth, JP & Gregory, JF (1996) Bioavilability for humans of deuterium-labeled monoglutamyl and polyglutamyl folates is affected by selected foods. Journal of Nutrition 126, 3100–3108.Google Scholar
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.Google Scholar
Witthöft, CM, Forssén, K, Johannesson, L & Jägerstad, M (1999) Folates –food sources, analyses, retention and bioavailability. Scandinavian Journal of Nutrition/Närinsforskning 43, 138–146.Google Scholar