Skip to main content

Bioavailability of lignans in human subjects

  • Thomas Clavel (a1) (a2), Joël Doré (a2) and Michael Blaut (a1)

Dietary lignans are phyto-oestrogens that possibly influence human health. The present review deals with lignan bioavailability, the study of which is crucial to determine to what extent metabolism, absorption and excretion of lignans alter their biological properties. Since intestinal bacteria play a major role in lignan conversion, for instance by producing the enterolignans enterodiol and enterolactone, emphasis is put on data obtained in recent bacteriological studies.

    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Bioavailability of lignans in human subjects
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Bioavailability of lignans in human subjects
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Bioavailability of lignans in human subjects
      Available formats
Corresponding author
*Corresponding author: Dr Michael Blaut, fax +49 0332 00 88 407, email
Hide All
Adlercreutz, H, Bannwart, C, Wahala, K, Makela, T, Brunow, G, Hase, T, Arosemena, PJ, Kellis, JT Jr & Vickery, LE (1993a) Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. Journal of Steroid Biochemistry and Molecular Biology 44, 147153
Adlercreutz, H, Fotsis, T, Kurzer, MS, Wahala, K, Makela, T & Hase, T (1995a) Isotope dilution gas chromatographic-mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces, with preliminary results in omnivorous and vegetarian women. Analytical Biochemistry 225, 101108
Adlercreutz, H, Fotsis, T, Lampe, J, Wahala, K, Makela, T, Brunow, G & Hase, T (1993b) Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Scandinavian Journal of Clinical and Laboratory Investigation 215, 518
Adlercreutz, H, van der Wildt, J, Kinzel, J, Attalla, H, Wahala, K, Makela, T, Hase, T & Fotsis, T (1995b) Lignan and isoflavonoid conjugates in human urine. Journal of Steroid Biochemistry and Molecular Biology 52, 97103
Adlercreutz, H, Wang, GJ, Lapcik, O, Hampl, R, Wahala, K, Makela, T, Lusa, K, Talme, M & Mikola, H (1998) Time-resolved fluoroimmunoassay for plasma enterolactone. Analytical Biochemistry 265, 208215
Andreasen, MF, Kroon, PA, Williamson, G & Garcia-Conesa, MT (2001) Intestinal release and uptake of phenolic antioxidant diferulic acids. Free Radical Biology and Medicine 31, 304314
Arts, IC, Sesink, AL, Faassen-Peters, M & Hollman, PC (2004) The type of sugar moiety is a major determinant of the small intestinal uptake and subsequent biliary excretion of dietary quercetin glycosides. British Journal of Nutrition 91, 841847
Aura, AM, Oikarinen, S, Mutanen, M, Heinonen, SM, Adlercreutz, HC, Virtanen, H & Poutanen, KS (2006) Suitability of a batch in vitro fermentation model using human faecal microbiota for prediction of conversion of flaxseed lignans to enterolactone with reference to an in vivo rat model. European Journal of Nutrition 45, 4551
Axelson, M & Setchell, KD (1980) Conjugation of lignans in human urine. FEBS Letters 122, 4953
Axelson, M & Setchell, KD (1981) The excretion of lignans in rats – evidence for an intestinal bacterial source for this new group of compounds. FEBS Letters 123, 337342
Axelson, M, Sjovall, J, Gustafsson, BE & Setchell, KD (1982) Origin of lignans in mammals and identification of a precursor from plants. Nature 298, 659660
Bannwart, C, Adlercreutz, H, Wahala, K, Brunow, G & Hase, T (1989) Detection and identification of the plant lignans lariciresinol, isolariciresinol and secoisolariciresinol in human urine. Clinica Chimica Acta 180, 293301
Begum, AN, Nicolle, C, Mila, I, Lapierre, C, Nagano, K, Fukushima, K, Heinonen, SM, Adlercreutz, H, Remesy, C & Scalbert, A (2004) Dietary lignins are precursors of mammalian lignans in rats. Journal of Nutrition 134, 120127
Bielefeldt, K, Waite, L, Abboud, FM & Conklin, JL (1996) Nongenomic effects of progesterone on human intestinal smooth muscle cells. American Journal of Physiology 271, G370G376
Boccardo, F, Lunardi, GL, Petti, AR & Rubagotti, A (2003) Enterolactone in breast cyst fluid: correlation with EGF and breast cancer risk. Breast Cancer Research and Treatment 79, 1723
Borriello, SP, Setchell, KD, Axelson, M & Lawson, AM (1985) Production and metabolism of lignans by the human faecal flora. Journal of Applied Bacteriology 58, 3743
Brooks, JD & Thompson, LU (2005) Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. Journal of Steroid Biochemistry and Molecular Biology 94, 461467
Brooks, JD, Ward, WE, Lewis, JE, Hilditch, J, Nickell, L, Wong, E & Thompson, LU (2004) Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. American Journal of Clinical Nutrition 79, 318325
Cho, JY, Kim, AR, Yoo, ES, Baik, KU & Park, MH (1999) Immunomodulatory effect of arctigenin, a lignan compound, on tumour necrosis factor-alpha and nitric oxide production, and lymphocyte proliferation. Journal of Pharmacy and Pharmacology 51, 12671273
Clavel, T, Borrmann, D, Braune, A, Doré, J & Blaut, M (2006a) Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 12, 140147
Clavel, T, Henderson, G, Alpert, C-A, Philippe, C, Rigottier-Gois, L, Dore, J & Blaut, M (2005) Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Applied and Environmental Microbiology 71, 60776085
Clavel, T, Henderson, G, Engst, W, Doré, J & Blaut, M (2006b) Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiology Ecology 55, 471478
Clavel T, Lippmann R, Gavini F, Doré J & Blaut M (2006c) Clostridium saccharogumia sp. nov. and Lactonifactor longoviformis gen. nov., sp. nov., two novel human faecal bacteria involved in the conversion of the dietary phytoestrogen secoisolariciresinol diglucoside. Systematic and Applied Microbiology (In the Press).
Dehennin, L, Reiffsteck, A, Jondet, M & Thibier, M (1982) Identification and quantitative estimation of a lignan in human and bovine semen. Journal of Reproduction and Fertility 66, 305309
Doerner, KC, Takamine, F, LaVoie, CP, Mallonee, DH & Hylemon, PB (1997) Assessment of fecal bacteria with bile acid 7 α-dehydroxylating activity for the presence of bai-like genes. Applied and Environmental Microbiology 63, 11851188
Feighner, SD & Hylemon, PB (1980) Characterization of a corticosteroid 21-dehydroxylase from the intestinal anaerobic bacterium. Eubacterium lentum. Journal of Lipid Research 21, 585593
Finegold, SM, Sutter, VL & Mathisen, GE (1983) Normal indigenous intestinal flora. In Human Intestinal Microflora in Health and Disease, pp. 331 [Henteges, DJ, editor]. New York: Academic Press
Ford, JD, Huang, KS, Wang, HB, Davin, LB & Lewis, NG (2001) Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed. Journal of Natural Products 64, 13881397
Grace, PB, Taylor, JI, Botting, NP, Fryatt, T, Oldfield, MF, Al-Maharik, N & Bingham, SA (2003) Quantification of isoflavones and lignans in serum using isotope dilution liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry 17, 13501357
Heinonen, S, Nurmi, T, Liukkonen, K, Poutanen, K, Wahala, K, Deyama, T, Nishibe, S & Adlercreutz, H (2001) In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. Journal of Agriculture and Food Chemistry 49, 31783186
Hong, SJ, Kim, SI, Kwon, SM, Lee, JR & Chung, BC (2002) Comparative study of concentration of isoflavones and lignans in plasma and prostatic tissues of normal control and benign prostatic hyperplasia. Yonsei Medical Journal 43, 236241
Horner, NK, Kristal, AR, Prunty, J, Skor, HE, Potter, JD & Lampe, JW (2002) Dietary determinants of plasma enterolactone. Cancer Epidemiology Biomarkers and Prevention 11, 121126
Hutchins, AM, Martini, MC, Olson, BA, Thomas, W & Slavin, JL (2000) Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Cancer Epidemiology Biomarkers and Prevention 9, 11131118
Jacobs, DR Jr, Pereira, MA, Stumpf, K, Pins, JJ & Adlercreutz, H (2002) Whole grain food intake elevates serum enterolactone. British Journal of Nutrition 88, 111116
Jacobs, E, Kulling, SE & Metzler, M (1999) Novel metabolites of the mammalian lignans enterolactone and enterodiol in human urine. Journal of Steroid Biochemistry and Molecular Biology 68, 211218
Jacobs, MN, Nolan, GT & Hood, SR (2005) Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicology and Applied Pharmacology 209, 123133
Jansen, GH, Arts, IC, Nielen, MW, Muller, M, Hollman, PC & Keijer, J (2005) Uptake and metabolism of enterolactone and enterodiol by human colon epithelial cells. Archives of Biochemistry and Biophysics 435, 7482
Juntunen, KS, Mazur, WM, Liukkonen, KH, Uehara, M, Poutanen, KS, Adlercreutz, HC & Mykkanen, HM (2000) Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women. British Journal of Nutrition 84, 839846
Kamal-Eldin, A, Peerlkamp, N, Johnsson, P, Andersson, R, Andersson, RE, Lundgren, LN & Aman, P (2001) An oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3-hydroxy-3-methyl glutaric acid residues. Phytochemistry 58, 587590
Kilkkinen, A, Stumpf, K, Pietinen, P, Valsta, LM, Tapanainen, H & Adlercreutz, H (2001) Determinants of serum enterolactone concentration. American Journal of Clinical Nutrition 73, 10941100
Kilkkinen, A, Valsta, LM, Virtamo, J, Stumpf, K, Adlercreutz, H & Pietinen, P (2003) Intake of lignans is associated with serum enterolactone concentration in Finnish men and women. Journal of Nutrition 133, 18301833
Knust, U, Hull, WE, Spiegelhalder, B, Bartsch, H, Strowitzki, T & Owen, RW (2006) Analysis of enterolignan glucuronides in serum and urine by HPLC-ESI-MS. Food and Chemical Toxicology 44, 10381049
Krafft, AE, Winter, J, Bokkenheuser, VD & Hylemon, PB (1987) Cofactor requirements of steroid-17–20-desmolase and 20 alpha-hydroxysteroid dehydrogenase activities in cell extracts of Clostridium scindens. Journal of Steroid Biochemistry and Molecular Biology 28, 4954
Kuijsten, A, Arts, IC, Van't Veer, P & Hollman, PC (2005a) The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed. Journal of Nutrition 135, 28122816
Kuijsten, A, Arts, IC, Vree, TB & Hollman, PC (2005b) Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. Journal of Nutrition 135, 795801
Kulling, SE, Jacobs, E, Pfeiffer, E & Metzler, M (1998) Studies on the genotoxicity of the mammalian lignans enterolactone and enterodiol and their metabolic precursors at various endpoints in vitro. Mutation Research 416, 115124
Kurzer, MS, Lampe, JW, Martini, MC & Adlercreutz, H (1995) Fecal lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. Cancer Epidemiology Biomarkers and Prevention 4, 353358
Lampe, JW, Gustafson, DR, Hutchins, AM, Martini, MC, Li, S, Wahala, K, Grandits, GA, Potter, JD & Slavin, JL (1999) Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake. Cancer Epidemiology Biomarkers and Prevention 8, 699707
Lampe, JW, Martini, MC, Kurzer, MS, Adlercreutz, H & Slavin, JL (1994) Urinary lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. American Journal of Clinical Nutrition 60, 122128
Liggins, J, Grimwood, R & Bingham, SA (2000) Extraction and quantification of lignan phytoestrogens in food and human samples. Analytical Biochemistry 287, 102109
Low, YL, Taylor, JI, Grace, PB, et al. . (2005) Polymorphisms in the CYP19 gene may affect the positive correlations between serum and urine phytoestrogen metabolites and plasma androgen concentrations in men. Journal of Nutrition 135, 26802686
McCann, MJ, Gill, CI, McGlynn, H & Rowland, IR (2005) Role of mammalian lignans in the prevention and treatment of prostate cancer. Nutrition and Cancer 52, 114
Mazur, WM (2000) Phytoestrogens: occurrence in foods, and metabolism of lignans in man and pigs. PhD Thesis, University of Helsinki
Mazur, WM, Uehara, M, Wahala, K & Adlercreutz, H (2000) Phyto-oestrogen content of berries, and plasma concentrations and urinary excretion of enterolactone after a single strawberry-meal in human subjects. British Journal of Nutrition 83, 381387
Milder, IE, Arts, IC, van de Putte, B, Venema, DP & Hollman, PC (2005a) Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. British Journal of Nutrition 93, 393402
Milder, IE, Feskens, EJ, Arts, IC, Bueno de Mesquita, HB, Hollman, PC & Kromhout, D (2005b) Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in Dutch men and women. Journal of Nutrition 135, 12021207
Morton, MS, Chan, PS, Cheng, C, Blacklock, N, Matos-Ferreira, A, Abranches-Monteiro, L, Correia, R, Lloyd, S & Griffiths, K (1997) Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom. Prostate 32, 122128
Nesbitt, PD, Lam, Y & Thompson, LU (1999) Human metabolism of mammalian lignan precursors in raw and processed flaxseed. American Journal of Clinical Nutrition 69, 549555
Niemeyer, HB, Honig, DM, Kulling, SE & Metzler, M (2003) Studies on the metabolism of the plant lignans secoisolariciresinol and matairesinol. Journal of Agriculture and Food Chemistry 51, 63176325
Nose, M, Fujimoto, T, Takeda, T, Nishibe, S & Ogihara, Y (1992) Structural transformation of lignan compounds in rat gastrointestinal tract. Planta Medica 58, 520523
Nurmi, T, Voutilainen, S, Nyyssonen, K, Adlercreutz, H & Salonen, JT (2003) Liquid chromatography method for plant and mammalian lignans in human urine. Journal of Chromatography 798B, 101110
Penalvo, JL, Heinonen, SM, Aura, AM & Adlercreutz, H (2005) Dietary sesamin is converted to enterolactone in humans. Journal of Nutrition 135, 10561062
Penalvo, JL, Nurmi, T, Haajanen, K, Al-Maharik, N, Botting, N & Adlercreutz, H (2004) Determination of lignans in human plasma by liquid chromatography with coulometric electrode array detection. Analytical Biochemistry 332, 384393
Phipps, WR, Martini, MC, Lampe, JW, Slavin, JL & Kurzer, MS (1993) Effect of flax seed ingestion on the menstrual cycle. Journal of Clinical Endocrinology and Metabolism 77, 12151219
Prasad, K (2005) Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis 179, 269275
Rickard, SE & Thompson, LU (1998) Chronic exposure to secoisolariciresinol diglycoside alters lignan disposition in rats. Journal of Nutrition 128, 615623
Saarinen, NM, Smeds, A, Makela, SI, Ammala, J, Hakala, K, Pihlava, JM, Ryhanen, EL, Sjoholm, R & Santti, R (2002) Structural determinants of plant lignans for the formation of enterolactone in vivo. Journal of Chromatography 777B, 311319
Setchell, KD & Adlercreutz, H (1988) Mammalian lignans and phyto-oestrogens – recent studies on their formation, metabolism and biological role in health and disease. In Role of the Gut Flora in Toxicity and Cancer, pp. 315345 [Rowland, IR, editor]. London: Academic Press
Setchell KD, Lawson AM, Axelson M & Adlercreutz H (1979) The excretion of two new phenolic compounds during the human menstrual cycle and in pregnancy. In Research on Steroids, vol. IX, pp. 207–215 [H Adlercreutz, RD Bulbrook, HJ Van der Molen, A Vermeulen and F Sciarra, editors]. Amsterdam, Oxford and Princeton: Excerpta Medica.
Setchell, KD, Lawson, AM, Conway, E, Taylor, NF, Kirk, DN, Cooley, G, Farrant, RD, Wynn, S & Axelson, M (1981) The definitive identification of the lignans trans-2,3-bis(3-hydroxybenzyl)-γ-butyrolactone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol in human and animal urine. Biochemical Journal 197, 447458
Shoda, J, He, BF, Tanaka, N, Matsuzaki, Y, Osuga, T, Yamamori, S, Miyazaki, H & Sjovall, J (1995) Increase of deoxycholate in supersaturated bile of patients with cholesterol gallstone disease and its correlation with de novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and small intestinal transit. Hepatology 21, 12911302
Sicilia, T, Niemeyer, HB, Honig, DM & Metzler, M (2003) Identification and stereochemical characterization of lignans in flaxseed and pumpkin seeds. Journal of Agriculture and Food Chemistry 51, 11811188
Smeds, AI, Hakala, K, Hurmerinta, TT, Kortela, L, Saarinen, NM & Makela, SI (2006) Determination of plant and enterolignans in human serum by high-performance liquid chromatography with tandem mass spectrometric detection. Journal of Pharmaceutical and Biomedical Analysis 41, 898905
Stitch, SR, Toumba, JK, Groen, MB, Funke, CW, Leemhuis, J, Vink, J & Woods, GF (1980) Excretion, isolation and structure of a new phenolic constituent of female urine. Nature 287, 738740
Stumpf, K, Pietinen, P, Puska, P & Adlercreutz, H (2000) Changes in serum enterolactone, genistein, and daidzein in a dietary intervention study in Finland. Cancer Epidemiology Biomarkers and Prevention 9, 13691372
Suau, A, Bonnet, R, Sutren, M, Godon, JJ, Gibson, GR, Collins, MD & Dore, J (1999) Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Applied and Environmental Microbiology 65, 47994807
Tarpila, S, Aro, A, Salminen, I, Tarpila, A, Kleemola, P, Akkila, J & Adlercreutz, H (2002) The effect of flaxseed supplementation in processed foods on serum fatty acids and enterolactone. European Journal of Clinical Nutrition 56, 157165
Thompson, LU, Chen, JM, Li, T, Strasser-Weippl, K & Goss, PE (2005) Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clinical Cancer Research 11, 38283835
Thompson, LU, Robb, P, Serraino, M & Cheung, F (1991) Mammalian lignan production from various foods. Nutrition and Cancer 16, 4352
Valentin-Blasini, L, Blount, BC, Caudill, SP & Needham, LL (2003) Urinary and serum concentrations of seven phytoestrogens in a human reference population subset. Journal of Exposure Analysis and Environmental Epidemiology 13, 276282
Walle, T, Browning, AM, Steed, LL, Reed, SG & Walle, UK (2005) Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. Journal of Nutrition 135, 4852
Wang, LQ, Meselhy, MR, Li, Y, Qin, GW & Hattori, M (2000) Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone. Chemical and Pharmaceutical Bulletin 48, 16061610
Ward, WE, Jiang, FO & Thompson, LU (2000) Exposure to flaxseed or purified lignan during lactation influences rat mammary gland structures. Nutrition and Cancer 37, 187192
Xia, ZQ, Costa, MA, Pelissier, HC, Davin, LB & Lewis, NG (2001) Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. Implications for human health protection. Journal of Biological Chemistry 276, 1261412623
Xie, LH, Ahn, EM, Akao, T, Abdel-Hafez, AA, Nakamura, N & Hattori, M (2003a) Transformation of arctiin to estrogenic and antiestrogenic substances by human intestinal bacteria. Chemical and Pharmaceutical Bulletin 51, 378384
Xie, LH, Akao, T, Hamasaki, K, Deyama, T & Hattori, M (2003b) Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chemical and Pharmaceutical Bulletin 51, 508515
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Nutrition Research Reviews
  • ISSN: 0954-4224
  • EISSN: 1475-2700
  • URL: /core/journals/nutrition-research-reviews
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed