Skip to main content

Dietary secoisolariciresinol diglucoside and its oligomers with 3-hydroxy-3-methyl glutaric acid decrease vitamin E levels in rats

  • Jan Frank (a1), Christina Eliasson (a1), Diane Leroy-Nivard (a1), Alicja Budek (a1), Torbjörn Lundh (a2), Bengt Vessby (a3), Per Åman (a1) and Afaf Kamal-Eldin (a1)...

Secoisolariciresinol diglucoside (SDG) is an important dietary lignan that is found at very high levels in flaxseed (1–4%, w/w). Flaxseed lignans have received much research interest in recent years because of reported phyto-oestrogenic, anticarcinogenic, and anti-atherogenic effects. Previously, flaxseed feeding has been shown to decrease vitamin E concentrations in rats despite the antioxidant potential of SDG in vitro. Sesamin, a sesame lignan, on the other hand has been shown to increase vitamin E concentrations in rats. The aim of the present study was to investigate the effect of dietary SDG and its oligomers on vitamin E and cholesterol concentrations in rats. SDG was extracted from defatted flaxseed flour with a dioxane–ethanol mixture and purified by silica column chromatography. The major oligomers with 3-hydroxy-3-methyl glutaric acid, containing a high ratio of SDG to p−coumaric and ferulic acid glucosides, were purified from the extracts by reversed-phase liquid chromatography. When fed to rats at 0·1% in the diet for 27%, both SDG and its oligomers had no effect on animal performance but caused an increase in liver cholesterol and a 2-fold reduction in the levels of α- and γ-tocopherols in rat plasma and liver. It is notable that a phenolic antioxidant, such as SDG, causes a vitamin E-lowering effect in rats. This cannot be explained at present, but warrants further investigations with respect to the magnitude, mechanism, and significance of the observed effect for human nutrition.

    • 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.

      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.

      Dietary secoisolariciresinol diglucoside and its oligomers with 3-hydroxy-3-methyl glutaric acid decrease vitamin E levels in rats
      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 Dropbox account. Find out more about sending content to Dropbox.

      Dietary secoisolariciresinol diglucoside and its oligomers with 3-hydroxy-3-methyl glutaric acid decrease vitamin E levels in rats
      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 Google Drive account. Find out more about sending content to Google Drive.

      Dietary secoisolariciresinol diglucoside and its oligomers with 3-hydroxy-3-methyl glutaric acid decrease vitamin E levels in rats
      Available formats
Corresponding author
*Corresponding author: fax +46 18 67 29 95, Email
Hide All
1Adlercreutz H, Fotsis T, Bannwart C, Wahala K, Makela T, Brunow G & Hase TDetermination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem 1986 25, 791797.
2Adlercreutz H, Fotsis T, Heikkinen R, Dwyer JT, Woods M, Goldin BR & Gorbach SLExcretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet 1982 ii, 12951299.
3Axelson M & Setchell KDThe excretion of lignans in rats – evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett 1981 123, 337342.
4Axelson M, Sjovall J, Gustafsson BE & Setchell KDOrigin of lignans in mammals and identification of a precursor from plants. Nature 1982 298, 659660.
5Bakke JE & Klosterman HJA new diglucoside from flaxseed. Proc North Dakota Acad Sci 1956 10, 1822.
6Bambagiotti-Alberti M, Coran SA, Ghiara C, Giannellini V & Raffaelli ARevealing the mammalian lignan precursor secoisolariciresinol diglucoside in flax seed by ionspray mass spectrometry. Rapid Commun Mass Spectrom 1994 a 8, 595598.
7Bambagiotti-Alberti M, Coron SA, Ghiara C, Moreti G & Raffaelli AInvestigation of mammalian lignan precursors in flax seed: first evidence of secoisolariciresinol diglucoside in two isomeric forms by liquid chromatograph/mass spectrometry. Rapid Commun Mass Spectrom 1994 b 8, 929932.
8Borriello SP, Setchell KD, Axelson M & Lawson AMProduction and metabolism of lignans by the human faecal flora. J Appl Bacteriol 1985 58, 3743.
9Eliasson C, Kamal-Eldin A, Andersson R & Åman PHPLC analysis of secoisolariciresinol diglucoside and hydroxycinnamic acid glucosides in flaxseed by alkaline extraction. J Chromatogr 2003 1012A, 151159.
10Ford JD, Huang KS, Wang HB, Davin LB & Lewis NGBiosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed. J Nat Prod 2001 64, 13881397.
11Frank J, Kamal-Eldin A, Lundh T, Määttä K, Törrönen R & Vessby BEffects of dietary anthocyanins on tocopherols and lipids in rats. J Agric Food Chem 2002 50, 72267230.
12Frank J, Kamal-Eldin A, Razdan A, Lundh T & Vessby BThe dietary hydroxycinnamate caffeic acid and its conjugate chlorogenic acid increase vitamin E and cholesterol concentrations in Sprague-Dawley rats. J Agric Food Chem 2003 a 51, 25262531.
13Frank J, Lundh T, Parker RS, Swanson JE, Vessby B & Kamal-Eldin Aietary (+)-catechin and BHT markedly increase alpha-tocopherol concentrations in rats by a tocopherol-omega-hydroxylase-independent mechanism. J Nutr 2003 b 133, 31953199.
14Gurbay A, Gonthier B, Daveloose D, Favier A & Hincal FMicrosomal metabolism of ciprofloxacin generates free radicals. Free Radic Biol Med 2001 30, 11181121.
15Hara A & Radin NSLipid extraction of tissues with a low-toxicity solvent. Anal Biochem 1978 90, 420426.
16Hensley K, Benaksas EJ & Bolli RNew perspectives on vitamin E: gamma-tocopherol and carboxyethylhydroxychroman metabolites in biology and medicine. Free Radic Biol Med 2004 36, 115.
17Jacobs E & Metzler MOxidative metabolism of the mammalian lignans enterolactone and enterodiol by rat, pig, and human liver microsomes. J Agric Food Chem 1999 47, 10711077.
18Jenab M & Thompson LUThe influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity. Carcinogenesis 1996 17, 13431348.
19Johnsson P, Kamal-Eldin A, Lundgren LN & Aman PHPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds. J Agric Food Chem 2000 48, 52165219.
20Johnsson P, Peerlkamp N, Kamal-Eldin A, Andersson RE, Andersson R, Lundgren LN & Åman PPolymeric fractions containing phenol glucosides in flaxseed. Food Chem 2001 76, 207212.
21Kamal-Eldin A, Frank J, Razdan A, Tengblad S, Basu S & Vessby BEffects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. Lipids 2000 35, 427435.
22Kamal-Eldin A, Peerlkamp N, Johnsson P, Andersson R, Andersson RE, Lundgren LN & Aman PAn oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3-hydroxy-3-methyl glutaric acid residues. Phytochemistry 2001 58, 587590.
23Klosterman HJ & Smith FThe isolation of β-hydroxy-β-methylglutaric acid from the seed of flax ( Linum usitatissimum). J Am Chem Soc 1954 76, 12291230.
24Klosterman HJ, Smith F & Clagett COThe constitution of linocinnamarin. J Am Chem Soc 1955 77, 420421.
25Laurenti O, Albi F, Artini M, Bravi C, Hurd R & Demattia GEffects of HMGA in non-insulin-dependent diabetics with secondary dyslipidemia. Clin Trials J 1990 27, 149154.
26Liggins J, Grimwood R & Bingham SAExtraction and quantification of lignan phytoestrogens in food and human samples. Anal Biochem 2000 287, 102109.
27Mazur W & Adlercreutz HNatural and anthropogenic environmental oestrogens: the scientific basis for risk assessment. Naturally occuring oestrogens in food. Pure Appl Chem 1998 70, 17591776.
28Meagher LP, Beecher GR, Flanagan VP & Li BWIsolation and characterization of the lignans, isolariciresinol and pinoresinol, in flaxseed meal. J Agric Food Chem 1999 47, 31733180.
29Nenadis N, Zhang HY & Tsimidou MZStructure-antioxidant activity relationship of ferulic acid derivatives: effect of carbon side chain characteristic groups. J Agric Food Chem 2003 51, 18741879.
30Nesbitt PD, Lam Y & Thompson LUHuman metabolism of mammalian lignan precursors in raw and processed flaxseed. Am J Clin Nutr 1999 69, 549555.
31Niemeyer HB & Metzler MOxidative metabolites and genotoxic potential of mammalian and plant lignans in vitro. J Chromatogr 2002 777, 321327.
32Paolini M, Antelli A, Pozzetti L, Spetlova D, Perocco P, Valgimigli L, Pedulli GF & Cantelli-Forti GInduction of cytochrome P450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats. Carcinogenesis 2001 22, 14831495.
33Prasad KHydroxy radical scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flaxseed. Mol Cell Biochem 1997 168, 117123.
34Prasad KReduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 1999 99, 13551362.
35Prasad K, Mantha SV, Muir AD & Westcott NDReduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis 1998 136, 367375.
36Qui SX, Lu ZZ, Luyengi L, Lee SK, Pezzuto JM, Farnsworth NR, Thompson LU & Fong HHSIsolation and characterization of flaxseed (Linum usitatissimum) constituents. Pharm Biol 1999 37, 17.
37Ratnayake WMN, Behrens WA, Fischer PWF, L'Abbé MR, Mongeau R & Beare-Rogers JLChemical and nutritional studies of flaxseed (variety Linott) in rats. J Nutr Biochem 1992 3, 232240.
38Rickard SE & Thompson LUChronic exposure to secoisolariciresinol diglycoside alters lignan disposition in rats. J Nutr 1998 128, 615623.
39Seigler L & Wu WTSeparation of serum high-density lipoprotein for cholesterol determination: ultracentrifugation vs precipitation with sodium phosphotungstate and magnesium chloride. Clin Chem 1981 27, 838841.
40Setchell KD, Lawson AM, Borriello SP, Harkness R, Gordon H, Morgan DM, Kirk DN, Adlercreatz H, Anderson LC & Axelson MLignan formation in man – microbial involvement and possible roles in relation to cancer. Lancet 1981 ii, 47
41Sicilia T, Niemeyer HB, Honig DM & Metzler MIdentification and stereochemical characterization of lignans in flaxseed and pumpkin seeds. J Agric Food Chem 2003 51, 11811188.
42Sontag TJ & Parker RSCytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem 2002 277, 2529025296.
43Thompson LU, Seidl MM, Rickard SE, Orcheson LJ & Fong HHAntitumorigenic effect of a mammalian lignan precursor from flaxseed. Nutr Cancer 1996 26, 159165.
44Westcott ND & Muir AD 1996 Process for extracting and purifiying lignans and cinnamic acid derivatives from flaxseed. PCT patent no. WO9630468A2.
45Westcott ND & Muir AD 1998 Process for extracting lignans from flaxseed. US patent no. 5.705.618.
46Westcott ND & Muir ADOverview of flax lignans. INFORM 2000 11, 118121.
47Wright JS, Johnson ER & DiLabio GAPredicting the activity of phenolic antioxidants: theoretical method, analysis of substituent effects, and application to major families of antioxidants. J Am Chem Soc 2001 123, 11731183.
Recommend this journal

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

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 59 *
Loading metrics...

Abstract views

Total abstract views: 115 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 18th November 2017. This data will be updated every 24 hours.