Skip to main content
Log in

Soy proteins and cardiovascular disease

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

The soybean diet is the most potent dietary tool for hypercholesterolemia. The United States Food and Drug Administration recently approved the health claim for its role in reducing the risk of coronary disease. The hypocholesterolemic effect is directly correlated to the patient’s cholesterolemia, with minimal or no reductions occurring at cholesterol of 6 mmol/L or less, and the most benefit occurring in patients with cholesterol of greater than 7 mmol/L. Hypotheses on the mechanism of action include soy fiber, isoflavones (phytoestrogens), and the protein itself. Although there is no evidence for the effect of fiber, studies with ethanol-extracted soy (devoid of isoflavones) indicated a loss of effect, but the extract itself (isoflavone rich) has no hypocholesterolemic activity. In humans, soy protein activates the low-density lipoprotein (LDL) receptor pathway. Recent data suggest that soy protein subunits, particularly 7S, directly activiate LDL receptors in the human liver, thus providing a novel mechanism of plasma cholesterol reduction different from currently available diets and hypolipidemic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Kim DN, Lee KT, Reiner JM, Thomas WA: Increased steroid excretion in swine fed high-fat high cholesterol diet with soy protein. Exp Mol Pathol 1980, 33:25–35.

    Article  PubMed  CAS  Google Scholar 

  2. Terpstra AH, Woodward CJ, West CE, Van Boven JG: A longitudinal cross-over study of serum cholesterol and lipoproteins in rabbits fed on semipurified diets containing either casein or soy-bean protein. Br J Nutr 1982, 47:213–219.

    Article  PubMed  CAS  Google Scholar 

  3. Sirtori CR, Lovati MR, Manzoni C, et al.: Reduction of serum cholesterol by soy proteins: clinical experience and potential molecular mechanisms. Nutr Metab Cardiovas Dis 1998, 8:334–340.

    CAS  Google Scholar 

  4. Van der Meer R, Beynen AC: Species-dependent responsiveness of serum cholesterol to dietary proteins. J Am Oil Chem Soc 1987, 64:1172–1177.

    Article  Google Scholar 

  5. Food and Drug Administration Web site. FDA approves soy health claim for food labels. Available at http://webmd.com/news/531891. Accessed September, 2000.

  6. Sirtori CR, Agradi E, Mantero O, et al.: Soybean protein diet in the treatment of type II hyperlipoproteinemia. Lancet 1977, i:275–277.

    Article  Google Scholar 

  7. Descovich G, Gaddi A, Mannino G, et al.: Multicenter study of soybean protein diet for outpatient hypercholesterolaemic patients. Lancet 1980, ii:709–712.

    Article  Google Scholar 

  8. Anderson JW, Bryan MJ, Cook-Newell ME: Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995, 333:276–282.

    Article  PubMed  CAS  Google Scholar 

  9. Gaddi A, Descovich GC, Noseda G, et al.: Hypercholesterolemia treated by soybean protein diet. Arch Dis Child 1987, 62:274–278.

    Article  PubMed  CAS  Google Scholar 

  10. Widhalm K, Brazda G, Schneider B, Kohl S: Effect of soy protein diet versus standard low fat, low cholesterol diet on lipid and lipoprotein levels in children with familial or polygenic hypercholesterolemia. J Pediatr 1993, 123:30–34.

    Article  PubMed  CAS  Google Scholar 

  11. D’Amico G, Gentile MG, Manna G, et al.: Effect of vegetarian soy diet on hyperlipidaemia in nephrotic syndrome. Lancet 1992, 339:1131–1134.

    Article  PubMed  CAS  Google Scholar 

  12. Sirtori CR: Tissue selectively of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Pharmac Ther 1993, 60:431–459.

    Article  CAS  Google Scholar 

  13. Pazzucconi F, Dorigotti F, Gianfranceschi G, et al.: Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity. Atherosclerosis 1995, 117:189–198.

    Article  PubMed  CAS  Google Scholar 

  14. Rubinstein A, Weintraub M: Escape phenomenon of 1 ow-density lipoprotein cholesterol during lovastatin treatment. Am J Cardiol 1995, 76:184–186.

    Article  PubMed  CAS  Google Scholar 

  15. Sirtori CR, Pazzucconi F, Colombo L, et al.: Double-blind study of the addition of high-protein soya milk v. cow’s milk to the diet of patients with severe hypercholesterolaemia and resistance to or intolerance of statins. Br J Nutr 1999, 82:91–96.

    PubMed  CAS  Google Scholar 

  16. Meinertz H, Nilausen K, Faergeman O: Soy protein and casein in cholesterol-enriched diets: effects on plasma lipoproteins in nomolipidemic subjects. Am J Clin Nutr 1989, 50:786–793.

    PubMed  CAS  Google Scholar 

  17. Potter SM, Bakhit RM, Essex-Sorlie DL, et al.: Depression of plasma cholesterol in men by consumption of baked products containing soy protein. Am J Clin Nutr 1993, 58:501–506.

    PubMed  CAS  Google Scholar 

  18. Jenkins DJ, Wolever TM, Spiller G, et al.: Hypocholesterolemic effect of vegetable protein in a hypocaloric diet. Atherosclerosis 1989, 78:99–107.

    Article  PubMed  CAS  Google Scholar 

  19. Fumagalli R, Soleri L, Musanti R, et al.: Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet. Atherosclerosis 1982, 43:341–353.

    Article  PubMed  CAS  Google Scholar 

  20. Duane WC: Effects of soybean protein and very low dietary cholesterol on serum lipids biliary lipids, and fecal sterols in humans. Metabolism 1999, 48:489–494.

    Article  PubMed  CAS  Google Scholar 

  21. Sirtori CR, Galli G, Lovati MR, et al.: Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats. J Nutr 1984, 114:1493–1500.

    PubMed  CAS  Google Scholar 

  22. Lovati MR, Manzoni C, Canavesi A, et al.: Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients. J Clin Invest 1987, 80:125–130.

    Article  Google Scholar 

  23. Gaddi A, Ciarocchi A, Matteuccci A, et al.: Dietary treatment for familial hypercholesterolemia - differential effects of dietary soy protein according to the apolipoprotein E phenotypes. Am J Clin Nutr 1991, 53:1191–1196.

    PubMed  CAS  Google Scholar 

  24. Anderson JW, Story L, Sieling B, et al.: Hypocholesterolemic effects of oat-bran or bean intake for hypercholesterolemic men. Am J Clin Nutr 1984, 40:1146–1155.

    PubMed  CAS  Google Scholar 

  25. Grundy SM, Bilheimer DW: Inhibition of 3-hydroxy-methyl glutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effect on cholesterol balance. Proc Natl Acad Sci USA 1984, 81:2538–2542.

    Article  PubMed  CAS  Google Scholar 

  26. Lusas EW, Riaz MN: Soy protein products: processing and use. J Nutr 1995, 125(suppl):573S-580S.

    PubMed  CAS  Google Scholar 

  27. Anthony MS, Clarkson TB, Hughes CL Jr, et al.: Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal Rhesus Monkeys. J Nutr 1996, 126:43–50.

    PubMed  CAS  Google Scholar 

  28. Wang HJ, Murphy PA: Isoflavone content in commercial soybean foods. J Agric Food Chem 1994, 42:1666–1673.

    Article  CAS  Google Scholar 

  29. Sirtori CR, Lovati MR, Manzoni C, et al.: Soy and cholesterol reduction: clinical experience. J Nutr 1995, 125(suppl):598S-605S.

    PubMed  CAS  Google Scholar 

  30. Sirtori CR, Gianazza E, Manzoni C, et al.: Role of isoflavones in the cholesterol reduction by soy proteins in the clinic. Am J Clin Nutr 1997, 65:166–167.

    PubMed  CAS  Google Scholar 

  31. Potter SM, Pertile J, Berbez-Jimenez MD: Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters. J Nutr 1996, 126:2007–2011.

    PubMed  CAS  Google Scholar 

  32. Brooks YR, Morr CV: Current aspects of soy protein fractionation and nomenclature. J Am Oil Chem Soc 1992, 62:1347–1354.

    Article  Google Scholar 

  33. Lovati MR, Manzoni C, Corsini A, et al.: Low density lipoprotein receptor activity is modulated by soybean globulins in cell culture. J Nutr 1992, 122:1971–1978.

    PubMed  CAS  Google Scholar 

  34. Lovati MR, Manzoni C, Gianazza E, Sirtori CR: Soybean protein products as regulators of liver low-density lipoprotein receptors. I. Identification of active b-conglycinin subunits. J Agric Food Chem 1998, 46:2474–2480.

    Article  CAS  Google Scholar 

  35. Manzoni C, Lovati MR, Gianazza E, Sirtori CR: Soybean protein products as regulators of liver low-density lipoprotein receptors. II. α-α’ rich commercial soy concentrate and α’ deficient mutant differently affect low-density lipoprotein receptor activation. J Agric Food Chem 1998, 46:2481–2484.

    Article  CAS  Google Scholar 

  36. Lovati MR, Manzoni C, Gianazza E, et al.: Soy protein peptides regulate cholesterol homeostasis in HepG2 cells. J Nutr 2000, 130:2543–2549.

    PubMed  CAS  Google Scholar 

  37. Adlercreutz H, Hoeckerstedt K, Bannwart C, et al.: Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG). J Steroid Biochem 1987, 27:1135–1144.

    Article  PubMed  CAS  Google Scholar 

  38. Adlercreutz H, Hamalainainen E, Gorbach S, Goldin B: Dietary phyto-estrogens and the menopause in Japan [letter]. Lancet 1992, 339:1233.

    Article  PubMed  CAS  Google Scholar 

  39. Cassidy A, Bingham S, Setchell KD: Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 1994, 60:333–340.

    PubMed  CAS  Google Scholar 

  40. Baird DD, Umbach DM, Lansdell L, et al.: Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab 1995, 80:1685–1690.

    Article  PubMed  CAS  Google Scholar 

  41. Xu X, Harris KS, Wang HJ, et al.: Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 1995, 125:2307–2315.

    PubMed  CAS  Google Scholar 

  42. Grove RI, Mazzucco CE, Radka SF, et al.: Oncostatin M up-regulates low density lipoprotein receptors in HepG2 cells by a novel mechanism. J Biol Chem 1991, 266:18194–18199.

    PubMed  CAS  Google Scholar 

  43. Wang HJ, Murphy P: Isoflavone content in commercial soybean foods. J Agric Food Chem 1994, 42:1666–1673.

    Article  CAS  Google Scholar 

  44. Lovati MR, Manzoni C, Agostinelli P, et al.: Studies on the mechanism of the cholesterol lowering activity of soy protein. Soy protein extract reduces plasma cholesterol and increases liver β-VLDL receptors in mice. Nutr Metab Cardiovasc Dis 1991, 1:18–24.

    CAS  Google Scholar 

  45. Crouse JR III, Morgan R, Terry JG, et al.: 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 Inter Med 1999, 159:2070–2076.

    Article  CAS  Google Scholar 

  46. Greaves KA, Parks JS, Williams JK, Wagner JD: 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.

    PubMed  CAS  Google Scholar 

  47. Greaves KT, Wilson MD, Rudel LL, et al.: Consumption of soy protein reduces cholesterol absorption compared to casein alone or supplemented with an isoflavone extract or conjugated equine estrogen in ovariectomized cynomolgous monkeys. J Nutr 2000, 130:820–826.

    PubMed  CAS  Google Scholar 

  48. Simons LA, von Konigsmark M, Simons J, Celermajer DS: Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol 2000, 85:1297–1301.

    Article  PubMed  CAS  Google Scholar 

  49. Ginsburg J, Prevelich GM: Lack of significant hormonal effects and controlled trials of phyto-oestrogens. Lancet 2000, 335:163–164.

    Article  Google Scholar 

  50. Sirtori CR: Dubious benefits and potential risk of soy phyto-oestrogens. Lancet 2000, 355:849.

    Article  PubMed  CAS  Google Scholar 

  51. Moundras C, Rèmèsy C, Levrat MA, Demignè C: Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein oxidizability. Metabolism 1995, 44:1146–1152.

    Article  PubMed  CAS  Google Scholar 

  52. Yusuf S, Anand S: Cost of prevention. The case of lipid lowering. Circulation 1996, 93:1774–1776.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sirtori, C.R., Lovati, M.R. Soy proteins and cardiovascular disease. Curr Atheroscler Rep 3, 47–53 (2001). https://doi.org/10.1007/s11883-001-0010-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-001-0010-2

Keywords

Navigation