Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-26T00:08:08.924Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women

Published online by Cambridge University Press:  01 August 2008

Sarah J. Blakesmith ,
Philippa M. Lyons–Wall ,
Caroline George ,
George E. Joannou ,
Peter Petocz  and
Samir Samman
Sarah J. Blakesmith
Affiliation:
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Australia
Philippa M. Lyons–Wall
Affiliation:
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Australia
Caroline George
Affiliation:
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Australia
George E. Joannou
Affiliation:
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Australia
Peter Petocz
Affiliation:
School of Mathematical Sciences, University of Technology, Australia
Samir Samman*
Affiliation:
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Australia
*
*Corresponding Author: Associate Professor Samir Samman, fax +61 2 93516022, 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.

Consumption of isoflavone-rich soyabean protein is reported to reduce total and LDL-cholesterol, but the specific components responsible are undetermined. In a previous crossover trial we showed that purified isoflavones, derived from red clover (Trifolium pratense), raised HDL3-cholesterol in premenopausal women; however, these findings were inconclusive due to period and carryover effects. In an attempt to overcome this problem, we utilised a parallel study designed to re-examine the effects of purified isoflavones on plasma lipoproteins and markers of insulin resistance in premenopausal women. Twenty-five healthy premenopausal women participated in a double-blind, randomised, parallel study. The treatment group (n 12) consumed a placebo for the first menstrual cycle and an isoflavone supplement (86 mg/d, derived from red clover) for three cycles, while the placebo group (n 13) consumed a placebo supplement for four menstrual cycles. Blood samples were collected weekly during cycles 1, 3 and 4. Supplementation with isoflavones resulted in a 15-fold increase in urinary isoflavone excretion (P<0·0001). There were no significant effects on total cholesterol, LDL- and HDL-cholesterol, HDL subfractions, triacylglycerol, lipoprotein(a), glucose or insulin concentrations. Our present results indicate that purified isoflavones derived from red clover have no effect on cholesterol homeostasis or insulin resistance in premenopausal women, a group which is at low risk of CHD.

Keywords

IsoflavonesLipidsPremenopausal women
Type
Research Article
Information
British Journal of Nutrition , Volume 89 , Issue 4 , April 2003 , pp. 467 - 474
Copyright
Copyright © The Nutrition Society 2003

References

Abbey, M, Owen, A, Suzakawa, M, Roach, P & Nestel, PJ (1999) Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity. Maturitas 33, 259–269.Google Scholar
Anderson, JW, Johnstone, BM & Cook-Newell, ME (1995) Meta-analysis of the effects of soy protein intake on serum lipids. New England Journal of Medicine 333, 276–282.Google Scholar
Anthony, MS, Clarkson, TB, Bullock, BC & Wagner, JD (1997) Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arteriosclerosis, Thrombosis and Vascular Biology 17, 2524–2531.Google Scholar
Anthony, MS, Clarkson, TB, Hughes, CL Jr, Morgan, TM & Burke, GL (1996) Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peri-pubertal rhesus monkeys. Journal of Nutrition 126, 43–50.CrossRefGoogle Scholar
Baum, JA, Teng, H, Erdman, JW Jr, Weigel, RM, Klein, BP, Persky, VW, Freels, S, Surya, P, Bakhit, RM, Ramos, E, Shay, NF & Potter, SM (1998) Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hyperchol-esterolemic, postmenopausal women. American Journal of Clinical Nutrition 68, 545–551.CrossRefGoogle ScholarPubMed
Brinton, EA (1996) Oral estrogen replacement therapy in postmenopausal women selectively raises levels and production rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate. Arteriosclerosis, Thrombosis and Vascular Biology 16, 431–440.Google Scholar
Carroll, KK (1991) Review of clinical studies on cholesterol-lowering response to soy protein. Journal of the American Dietetic Association 91, 820–827.Google Scholar
Cassidy, A, Bingham, S & Setchell, KD (1994) Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. American Journal of Clinical Nutrition 60, 333–340.Google Scholar
Cassidy, A, Bingham, S & Setchell, K (1995) Biological effects of isoflavones in young women: importance of the chemical composition of soyabean products. British Journal of Nutrition 74, 587–601.CrossRefGoogle ScholarPubMed
Crouse, JR, Morgan, T, Terry, JG, Ellis, J, Vitolins, M & Burke, GL (1999) A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Archives of Internal Medicine 159, 2070–2076.Google Scholar
Dahlen, GH (1994) Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis 108, 111–126.Google Scholar
Franke, AA, Custer, LJ, Cerna, CM & Narala, K (1995) Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine. Proceedings of the Society for Experimental Biology and Medicine 208, 18–26.Google Scholar
Friedewald, WT, Levy, RI & Friedrickson, DS (1972) Estimation of the concentrations of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry 18, 499–502.Google Scholar
Greaves, KA, Parks, JS, Williams, JK & Wagner, JD (1999) Intact dietary soy protein, but not adding an isoflavone-rich soy extract to casein, improves plasma lipids in ovariectomized cynomolgus monkeys. Journal of Nutrition 129, 1585–1592.CrossRefGoogle Scholar
Haines, C, Chung, T, Chang, A, Masarei, J, Tomlinson, B & Wong, E (1996) Effects of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. Archives of Internal Medicine 156, 866–872.CrossRefGoogle ScholarPubMed
Hodgson, JM, Puddey, IB, Beilin, LJ, Mori, TA & Croft, KD (1998) Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. Journal of Nutrition 128, 728–732.Google Scholar
Howes, JB, Sullivan, D, Lai, N, Nestel, P, Pomeroy, P, West, L, Eden, JA & Howes, LG (2000) The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholes-terolaemia. Atherosclerosis 152, 143–147.Google Scholar
Joannou, GE, Kelly, GE, Reeder, AY, Waring, M & Nelson, C (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. Journal of Steroid Biochemistry and Molecular Biology 54, 167–184.Google Scholar
Kanuck, MP & Ellworth, JL (1995) Tyrosine kinase inhibitors potentiate the induction of low-density lipoprotein receptor gene expression by hepatocyte growth factor. Life Sciences 57, 1981–1991.Google Scholar
Kelly, GE, Joannou, GE, Reeder, AY, Nelson, C & Waring, M (1995) The variable metabolic response to dietary isoflavones in humans. Proceedings of the Society for Experimental Biology and Medicine 208, 40–43.Google ScholarPubMed
Khosla, P, Samman, S & Carroll, KK (1991) Decreased receptor-mediated LDL catabolism in casein-fed rabbits preceded the increase in plasma cholesterol levels. Journal of Nutritional Biochemistry 2, 203–209.Google Scholar
Kirk, EA, Sutherland, P, Wang, SA, Chait, A & LeBoeuf, RC (1998) Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. Journal of Nutrition 128, 954–959.CrossRefGoogle Scholar
Lamon-Fava, S (2000) Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line Hep G2. Journal of Nutrition 130, 2489–2492.Google Scholar
Lamon-Fava, S, Ordovas, JM & Schaefer, EJ (1999) Estrogen increases apolipoprotein (apo) A-I secretion in hep G2 cells by modulating transcription of the apo A-I gene promoter. Arteriosclerosis, Thrombosis and Vascular Biology 19, 2960–2965.CrossRefGoogle ScholarPubMed
Lovati, MR, Manzoni, C, Gianazza, E, Arnoldi, A, Kurowska, E, Carroll, KK & Sirtori, CR (2000) Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells. Journal of Nutrition 130, 2543–2549.Google ScholarPubMed
Lyons, Wall PM, Choudury, N, Gerbrandy, EA & Truswell, A (1994) Increase of high-density lipoprotein cholesterol at ovulation in healthy women. Atherosclerosis 105, 171–178.CrossRefGoogle Scholar
Markiewicz, L, Garey, J, Adlercreutz, H & Gurpide, E (1993) In vitro bioassay of non-steroidal phytoestrogens. Journal of Steroid Biochemistry 45, 399–405.Google Scholar
Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF & Turner, RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419.CrossRefGoogle ScholarPubMed
Merz-Demlow, BE, Duncan, AM, Wangen, KE, Xu, X, Carr, TP, Phipps, WR & Kurzer, MS (2000) Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. American Journal of Clinical Nutrition 71, 1462–1469.Google Scholar
Milligan, SR, Balasubramanian, AV & Kalita, JC (1998) Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay. Environmental Health Perspectives 106, 23–26.CrossRefGoogle Scholar
Muesing, RA, Miller, VT, LaRosa, JC, Stoy, DB & Phillips, EA (1992) Effects of unopposed conjugated equine estrogen on lipoprotein composition and apolipoprotein-E distribution. Journal of Clinical Endocrinology and Metabolism 75, 1250–1254.Google ScholarPubMed
Nagata, C, Kabuto, M, Kurisu, Y & Shimizu, H (1997) Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women. Nutrition and Cancer 29, 228–233.Google Scholar
Nestel, PJ, Pomeroy, S, Kay, S, Komesaroff, P, Behrsing, J, Cameron, JD & West, L (1999) Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. Journal of Clinical Endocrinology and Metabolism 84, 895–898.Google Scholar
Nestel, PJ, Yamashita, T, Sasahara, T, Pomeroy, S, Dart, A, Komesaroff, P, Owen, A & Abbey, M (1997) Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arteriosclerosis, Thrombosis and Vascular Biology 17, 3392–3398.Google Scholar
Nilausen, K & Meinertz, H (1999) Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein. American Journal of Clinical Nutrition 69, 419–425.Google Scholar
Potter, SM (1998) Soy protein and cardiovascular disease: the impact of bioactive components in soy. Nutrition Reviews 56, 231–235.Google Scholar
Samman, S, Lyons, Wall PM, Chan, GS, Smith, SJ & Petocz, P (1999) The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women. Atherosclerosis 147, 277–283.Google Scholar
Samman, S & Truswell, A (1993) The Friedewald equation for the determination of low density lipoprotein cholesterol: a special case. American Journal of Clinical Nutrition 58, 928–929.Google Scholar
Simons, LA, von Konigsmark, M, Simons, J & Celermajer, DS (2000) Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy postmenopausal women. American Journal of Cardiology 85, 1297–1301.Google Scholar
Sirtori, CR, Gianazza, E, Manzoni, C, Lovati, MR & Murphy, PA (1997) Role of isoflavones in the cholesterol reduction by soy proteins in the clinic. American Journal of Clinical Nutrition 65, 166–167.CrossRefGoogle ScholarPubMed
Tikkanen, MJ (1996) Estrogens, progestins and lipid metabolism. Maturitas 23S, 51–55.CrossRefGoogle ScholarPubMed
Warnick, GR, Benderson, J & Albers, J (1982) Dextran sulfate–Mg2+ precipitation procedure for quantification of high-density lipoprotein cholesterol. Clinical Chemistry 28, 1379–1388.CrossRefGoogle Scholar