Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects


      To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62±9 years, BMI 26±3 kg/m2, LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24 h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P<0.0001), total cholesterol by 4.4% (P<0.001), and LDL cholesterol by 5.7% (P=0.003) compared to animal protein. The TGFA-FSR was reduced by13.3% (P=0.018) and FC-FSR was increased by 7.6% (P=0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P=0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Anderson J.W
        • Johnston B.M
        • Cook-Newell M.E
        Meta-analysis of the effects of soy protein intake on serum lipids.
        New Engl. J. Med. 1995; 333: 276-282
        • Baum J.A
        • Teng H
        • Erdman J.W
        • Weigel R.M
        • Klein B.P
        • Persky V.W
        • et al.
        Long-term intake of soy protein lowers the risk of cardiovascular disease and increases mononuclear cell LDL receptor mRNA in hypercholesterolemic postmenopausal women.
        Am. J. Clin. Nutr. 1998; 68: 545-551
        • Nilausen K
        • Meinertz H
        Variable lipemic response to dietary soy protein in healthy, normolipemic men.
        Am. J. Clin. Nutr. 1998; 68: 1380S-1384S
        • Crouse J.R
        • Morgan T
        • Terry J.G
        • Ellis J
        • Vitolins M
        • Burke G.L
        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.
        Arch. Int. Med. 1999; 159: 2070-2076
        • Duane W.C
        Effects of soybean protein and very low dietary cholesterol on serum lipids, biliary lipids, and fecal sterols in humans.
        Metabolism. 1999; 48: 489-494
        • Teede H.J
        • Dalais F.S
        • Kotsopoulos D
        • Liang Y.L
        • Davis S
        • McGrath B.P
        Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women.
        J. Clin. Endocrinol. Metab. 2001; 86: 3053-3060
        • Teixeira S.R
        • Potter S.M
        • Weigel R
        • Hannum S
        • Erdman Jr, J.W
        • Hasler C.M
        Effects of feeding levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men.
        Am. J. Clin. Nutr. 2000; 71: 1077-1084
        • Gardner C.D
        • Newell K.A
        • Cherin R
        • Haskell W
        The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women.
        Am. J. Clin. Nutr. 2001; 73: 728-735
        • Potter S.M
        Soy protein and cardiovascular disease: the impact of bioactive components in soy.
        Nutr. Rev. 1998; 56: 231-235
        • Greaves K.A
        • Wilson M.D
        • Rudel L.L
        • Williams J.K
        • Wagner J.D
        Consumption of soy protein reduces cholesterol absorption compared to casein alone or supplemented with an isoflavone extract or conjugated equine estrogen in ovariectomized cynomolgus monkeys.
        J. Nutr. 2000; 30: 820-826
        • Huff M.W
        • Carroll K.K
        Effects of dietary protein on turnover, oxidation, and absorption of cholesterol and on steroid excretion in rabbits.
        J. Lipid Res. 1980; 21: 546-548
        • Nagata Y
        • Ishiwaki N
        • Sugano M
        Studies on the mechanism of antihypercholesterolemic action of soy protein and soy protein-type amino acid mixtures in relation to the casein counterparts in rats.
        J. Nutr. 1982; 112: 1614-1625
        • Khosla P
        • Samman S
        • Carroll K.K
        Decreased receptor-mediated LDL catabolism in casein-fed rabbits precedes the increase in plasma cholesterol levels.
        J. Nutr. Biochem. 1991; 2: 203-209
        • Sirtori C.R
        • Galli G
        • Lovati M.R
        • Carrara P
        • Bosisio E
        • Kienle M.G
        Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats.
        J. Nutr. 1984; 114: 1493-1500
        • Lovati M.R
        • Manzoni C
        • Canavesi A
        • Sirtori M
        • Vaccarino V
        • Marchi M
        • et al.
        Soybean protein diet increases low-density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients.
        J. Clin. Invest. 1987; 80: 1498-1502
        • Wright S.M
        • Salter A.M
        Effects of soy protein on plasma cholesterol and bile acid excretion in hamsters.
        Comp. Biochem. Physiol. 1998; 119B: 247-254
        • Potter S.M
        Soy protein and serum lipids.
        Curr. Opin. Lipidol. 1996; 7: 260-264
        • Madani S
        • Prost J
        • Belleville J
        Dietary protein level and origin (casein and highly purified soybean protein) affect hepatic storage, plasma lipid transport, and antioxidative defense status in the rat.
        Nutrition. 2000; 16: 368-375
        • Peluso M.R
        • Winters T.A
        • Shanahan M.F
        • Banz W.J
        A cooperative interaction between soy protein and its isoflavone-enriched fraction lowers hepatic lipids in male obese Zucker rats and reduces blood platelet sensitivity in male Sprague–Dawley rats.
        J. Nutr. 2000; 130: 2333-2342
        • Potter S.M
        • Baum J.A
        • Teng H
        • Stillman R.J
        • Shay N.F
        • Erdman Jr, J.W
        Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.
        Am. J. Clin. Nutr. 1998; 68: 1375S-1379S
      1. Food labeling. Health claims: soy protein and coronary heart disease; final rule. Fed. Register 1999;64:57700–33.

        • Nestel P.J
        • Yamashita T
        • Sasahara T
        • Chin-Dusting P.J
        • Esler M.D
        • Dart A.M
        • et al.
        Soy isoflavones improve arterial compliance but not plasma lipoids in menopausal and perimenopausal women.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 3392-3398
        • Hodgson J.M
        • Puddey I.B
        • Beilin L.J
        • Mori T.A
        • Croft K.D
        Supplementation with isoflavonoid phytoestrogens does not alter lipid concentrations: a randomized controlled trial in humans.
        J. Nutr. 1998; 128: 728-732
        • Simons L.A
        • von Konigsmark M
        • Simons J
        • Celermajer D.S
        Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women.
        Am. J. Cardiol. 2000; 85: 1297-1301
        • Nestel P.J
        • Pomeroy S
        • Kay S
        • Komesaroff P
        • Behrsing J
        • Cameron D.L
        • et al.
        Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women.
        J. Clin. Endocrinol. Metab. 1999; 84: 895-898
        • Lichtenstein A.H
        • Jalbert S.M
        • Adlercreutz H
        • Goldin B.R
        • Rasmussen H
        • Schaefer E.J
        • et al.
        Lipoprotein response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects.
        ATVB. 2002; 22: 1852-1858
        • McNamara J.R
        • Schaefer E.J
        Automatic enzymatic standardized lipid analyses for plasma and lipoprotein fractions.
        Clin. Chim. Acta. 1987; 166: 1-8
        • Warnick G.R
        • Benderson J
        • Albers J.J
        Dextran sulfate-Mg++ precipitation procedure for quantitation of high density lipoprotein cholesterol.
        Clin. Chem. 1982; 28: 1379-1388
        • Jones P.J.H
        • Dendy S.M
        • Frohlich J.J
        • Leitch C.A
        • Schoeller D.A
        Cholesterol and triglyceride fatty acid synthesis in apolipoprotein E2-associated hyperlipidemia.
        Arterioscler. Thromb. 1992; 12: 106-113
        • Konrad S.D
        • Cook C.L
        • Goh Y.K
        • French M.A
        • Clandinin M.T
        Use of deuterium oxide to measure de novo fatty acid synthesis in normal subjects consuming different dietary fatty acid composition.
        Biochim. Biophys. Acta. 1998; 1393: 143-152
        • Schoeller D.A
        • Peterson D.W
        • Hayes J.M
        Double-comparison method for mass spectrometric determination of hydrogen isotope abundances.
        Anal. Chem. 1983; 55: 827-832
      2. SAS User’s Guide: Statistics, Version 6.12. SAS Institute Inc., Cary, NC, 1990.

        • Bakhit R.M
        • Klein B.P
        • Essex-Sorlie D
        • Ham J.O
        • Erdman Jr, J.W
        • Potter S.M
        Intake of 25 g of soybean protein with or without soybean fiber alters plasma lipids in men with elevated cholesterol concentrations.
        J. Nutr. 1994; 124: 213-222
        • Greaves K.A
        • Parks J.S
        • Williams J.K
        • Wagner J.D
        Intact dietary soy protein, but not adding an isoflavone-rich soy extract to casein, improves plasma lipids in ovariectomized cynomolgus monkeys.
        J. Nutr. 1999; 129: 1585-1592
        • Chiechi L.M
        • Secreto G
        • Vimercati A
        • Greco P
        • Venturelli E
        • Pansini F
        • et al.
        The effects of a soy rich diet on serum lipids: the Menfis randomized trial.
        Maturitas. 2002; 41: 97-104
        • Maddox D.A
        • Alavi F.K
        • Silbernick E.M
        • Zawada E.T
        Protective effects of a soy diet in preventing obesity-linked renal disease.
        Kidney Int. 2002; 61: 96-104
        • Sirtori C.R
        • Bosisio R
        • Pazzucconi F
        • Bondioli A
        • Gatti E
        • Lovati M.R
        • et al.
        Soy milk with a high glycitein content does not reduce low-density lipoprotein cholesterolemia in type II hypercholesterolemic patients.
        Ann. Nutr. Metab. 2002; 46: 88-92
        • Potter S.M
        Overview of proposed mechanisms for the hypocholesterolemic effect of soy.
        J. Nutr. 1995; 125: 606S-611S
        • Nagaoka S
        • Miwa K
        • Eto M
        • Kuzuya Y
        • Hori G
        • Yamamoto K
        Soy protein peptic hydrolysate with bound phospholipids decreases micellar solubility and cholesterol absorption in rats and Caco-2 cells.
        J. Nutr. 1999; 129: 1725-1730
        • Ntanios F.Y
        • Jones P.J
        Dietary sitostanol reciprocally influences cholesterol absorption and biosynthesis in hamsters and rabbits.
        Atherosclerosis. 1999; 143: 341-351
        • Jones P.J.H
        • Raeini-Sarjaz M
        • Ntanios F.Y
        • Vanstone C.A
        • Feng J.Y
        • Parsons W.E
        Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters.
        J. Lipid Res. 2000; 41: 697-705
        • Sirtori C.R
        • Lovati M.R
        • Manzoni C
        • Monetti M
        • Pazzucconi F
        • Gatti E
        Soy and cholesterol reduction: clinical experience.
        J. Nutr. 1995; 125: 598S-605S
        • Urban D
        • Irwin W
        • Kirk M
        • Markiewicz M.A
        • Myers R
        • Smith M
        • et al.
        The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen.
        J. Urol. 2001; 165: 294-300
        • Wangen K.E
        • Duncan A.M
        • Xu X
        • Kurzer M.S
        Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women.
        Am. J. Clin. Nutr. 2001; 73: 225-231
        • Howes J.B
        • Sullivan D
        • Lai N
        • Nestel P
        • Pomeroy S
        • West L
        • et al.
        The effect of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolemia.
        Atherosclerosis. 2001; 152: 143-147
        • Dewell A
        • Hollenbeck C.B
        • Bruce B
        The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women.
        J. Clin. Endocrinol. Metab. 2002; 87: 118-121