Amino Acids

, Volume 38, Issue 1, pp 15–22 | Cite as

Alimentary proteins, amino acids and cholesterolemia

  • François Blachier
  • Antonio H. LanchaJr
  • Claire Boutry
  • Daniel Tomé
Review Article


Numerous data from both epidemiological and experimental origins indicate that some alimentary proteins and amino acids in supplements can modify the blood LDL cholesterol, HDL cholesterol and total cholesterol. After an initial approval of the health claim for soy protein consumption for the prevention of coronary heart disease, more recently it has been concluded from an overall analysis of literature that isolated soy protein with isoflavones only slightly decrease LDL and total cholesterol. Other plant extracts and also some proteins from animal origin have been reported to exert a lowering effect on blood cholesterol when compared with a reference protein (often casein). The underlying mechanisms are still little understood. Individual amino acids and mixture of amino acids have also been tested (mostly in animal studies) for their effects on cholesterol parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine, aspartate and glutamate have been tested individually and in combination in different models of either normo or hypercholesterolemic animals and found to be able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol. It is however not known if these results are relevant to human nutrition.


Alimentary proteins Amino acid supplementation Cholesterol 


  1. Adams MR, Golden DL, Anthony MS, Register TC, Williams JK (2002) The inhibitory effect of soy protein on atherosclerosis in mice does not require the presence of LDL receptor or alteration of plasma lipoproteins. J Nutr 132:43–49PubMedGoogle Scholar
  2. Adams MR, Golden DL, Franke AA, Potter SM, Smith HS, Anthony MS (2004) Dietary soy beta-conglycinin (7S globulin) inhibits atherosclerosis in mice. J Nutr 134:511–516PubMedGoogle Scholar
  3. Anderson JW, Johnstone BM, Cook-Newell ME (1995) Meta-analysis of the effects of soy protein on serum lipids. N Engl J Med 333:276–282. doi: 10.1056/NEJM199508033330502 CrossRefPubMedGoogle Scholar
  4. Anderson JW, Smith B, Washnock CS (1999) Cardiovascular and renal benefits of dry bean and soybean intake. Am J Clin Nutr 70:464S–474SPubMedGoogle Scholar
  5. Anthony MS, Clarkson TB, Williams JK (1998) Effects of soy isoflavones on atherosclerosis:potential mechanisms. Am J Clin Nutr 68:1390S–1393SPubMedGoogle Scholar
  6. Aoyama Y, Amano N, Yoshida A (1999) Cholesterol synthesis and degradation in normal rats fed a cholesterol-free diet with excess cystine. Lipids 34:583–589. doi: 10.1007/s11745-999-0402-8 CrossRefPubMedGoogle Scholar
  7. Baum JA, Teng H, Erdman JW, 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 hypercholesterolemic, postmenopausal women. Am J Clin Nutr 68:545–551PubMedGoogle Scholar
  8. Belleville J (2002) Hypocholesterolemic effect of soy protein. Nutrition 18:684–686. doi: 10.1016/S0899-9007(02)00799-2 CrossRefPubMedGoogle Scholar
  9. Bloch K (1944) Some aspects of the metabolism of leucine and valine. J Biol Chem 115:255–263Google Scholar
  10. Carroll KK (1981) Dietary protein and cardiovascular disease. In: New trends in nutrition, Lipid research and cardiovascular diseases. Alan Liss Inc., New YorkGoogle Scholar
  11. Choi YY, Osada K, Ito Y, Nagasawa T, Choi MR, Nishizawa N (2005) Effects of dietary protein of Korean foxtail millet on plasma adiponectin, HDL-cholesterol, and insulin levels in genetically type 2 diabetic mice. Biosci Biotechnol Biochem 69:31–37. doi: 10.1271/bbb.69.31 CrossRefPubMedGoogle Scholar
  12. Choi MJ, Kim JH, Chang KJ (2006) The effect of dietary taurine supplementation on plasma and liver lipid concentrations and free amino acid concentrations in rats fed a high-cholesterol diet. Adv Exp Med Biol 583:235–242. doi: 10.1007/978-0-387-33504-9_25 CrossRefPubMedGoogle Scholar
  13. Crouse JR, Morgan T, Terry JG, Ellis G, Vitolons M, Burke GL (1999) A randomised trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med 159:2070–2076. doi: 10.1001/archinte.159.17.2070 CrossRefPubMedGoogle Scholar
  14. Cuevas AM, Irribarra VL, Castillo OA, Yanez MD (2003) Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. Eur J Clin Nutr 57:889–894. doi: 10.1038/sj.ejcn.1601622 CrossRefPubMedGoogle Scholar
  15. Debry G (2004) Experimental data on animals: dietary proteins and atherosclerosis. CRC, West Palm BeachGoogle Scholar
  16. Francis G, Kerem Z, Makkar HP, Becker K (2002) The biological action of saponins in animal systems: a review. Br J Nutr 88:587–605. doi: 10.1079/BJN2002725 CrossRefPubMedGoogle Scholar
  17. Friedman M, Brandon DL (2001) Nutritional and health benefits of soy proteins. J Agric Food Chem 49:1069–1086. doi: 10.1021/jf0009246 CrossRefPubMedGoogle Scholar
  18. Giroux I, Kurowska EM, Carroll KK (1999) Role of dietary lysine, methionine, and arginine in the regulation of hypercholesterolemia in rabbits. J Nutr Biochem 10:166–171. doi: 10.1016/S0955-2863(98)00091-6 CrossRefPubMedGoogle Scholar
  19. Hidiroglou N, Gilani GS, Long L, Zhao X, Madere R, Cockell K, Belonge B, Ratnayake WM, Peace R (2004) The influence of dietary vitamin E, fat, and methionine on blood cholesterol profile, homocysteine levels, and oxidizability of low-density lipoprotein in the gerbil. J Nutr Biochem 15:730–740. doi: 10.1016/j.jnutbio.2004.04.009 CrossRefPubMedGoogle Scholar
  20. Hirche F, Schröder A, Knoth GI, Stangl GI, Eder K (2006) Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism. Br J Nutr 95:879–888. doi: 10.1079/BJN20061729 CrossRefPubMedGoogle Scholar
  21. Hodges RE, Krehl WA, Stone DB, Lopez A (1967) Dietary carbohydrates and low cholesterol diets: effects on serum lipids on man. Am J Clin Nutr 20:198–208PubMedGoogle Scholar
  22. Horigome T, Cho YS (1992) Dietary casein and soybean protein affect the concentrations of serum cholesterol, triglycerides and free amino acids in rats. J Nutr 122:2273–2282PubMedGoogle Scholar
  23. Huff MW, Hamilton RMG, Carroll KK (1977) Effects of dietary proteins and amino acids on the plasma cholesterol concentrations of rabbits fed cholesterol-free diets. Adv Exp Med Biol 82:275–277PubMedGoogle Scholar
  24. Jacques H, Gascon A, Bergeron N, Lavigne C, Hurley C, Deshaies Y, Moorjani S, Julien P (1995) Role of dietary fish protein in the regulation of plasma lipids. Can J Cardiol G:63G–71GGoogle Scholar
  25. Kern M, Ellison D, Marroquin Y, Ambrose M, Mosier K (2002) Effects of soy protein supplemented with methionine on blood lipids and adiposity of rats. Nutrition 18:654–656. doi: 10.1016/S0899-9007(02)00783-9 CrossRefPubMedGoogle Scholar
  26. Kurowska EM, Carroll KK (1990) Essential amino acids in relation to hypercholesterolemia induced in rabbits by dietary casein. J Nutr 120:831–836PubMedGoogle Scholar
  27. Kurowska EM, Carroll KK (1992) Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits. Biochim Biophys Acta 1126:185–191PubMedGoogle Scholar
  28. Kurowska EM, Carroll KK (1994) Hypercholesterolemic responses in rabbits to selected groups of dietary essential amino acids. J Nutr 124:364–370PubMedGoogle Scholar
  29. Kurowska EM, Carroll KK (1996) LDL versus apolipoprotein B responses to variable proportions of selected amino acids in semipurified diets fed to rabbits and in the media of hepG2 cells. J Nutr Biochem 7:418–424. doi: 10.1016/0955-2863(96)00064-2 CrossRefGoogle Scholar
  30. Kurowska EM, Hrabek-Smith JM, Carroll KK (1989) Compositional changes in serum lipoproteins during development of casein-induced hypercholesterolemia in rabbits. J Nutr 116:1395–1404Google Scholar
  31. Lin Y, Meijer GW, Vermeer MA, Trautwein EA (2004) Soy protein enhances the cholesterol-lowering effect of plant sterol esters in cholesterol-fed hamsters. J Nutr 134:143–148PubMedGoogle Scholar
  32. Matthews DE, Bier DM, Rennie MJ, Edwards RH, Halliday D, Millward DJ, Clugston GA (1981) Regulation of leucine metabolism in man: a stable isotope study. Science 214:1129–1131. doi: 10.1126/science.7302583 CrossRefPubMedGoogle Scholar
  33. Mayilvaganan M, Singh SP, Johari RP (2004) Hypocholesterolemic effect of protein prepared from Phaseolus aconitifolius (Jacq.). Indian J Exp Biol 42:904–908PubMedGoogle Scholar
  34. McCarty (1999) Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity. Med Hypotheses 53:459–485. doi: 10.1054/mehy.1999.0784 CrossRefPubMedGoogle Scholar
  35. Morita T, Oh-Hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S (1997) Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr 127:470–477PubMedGoogle Scholar
  36. Moriyama T, Kishimoto K, Nagai K, Urade R, Ogawa T, Utsumi S, Maruyama N, Maebuchi M (2004) Soybean beta-conglycinin diet suppresses serum triglyceride levels in normal and genetically obese mice by induction of beta-oxidation, downregulation of fatty acid synthase, and inhibition of triglyceride absorption. Biosci Biotechnol Biochem 68:352–359. doi: 10.1271/bbb.68.352 CrossRefPubMedGoogle Scholar
  37. Nagaoka S, Kanamaru Y, Kuzuya Y (1991) Effects of whey protein and casein on the plasma and liver lipids in rats. Agric Biol Chem 55:813–818Google Scholar
  38. Nagaoka S, Kanamaru Y, Kuzuya Y, Kojima S (1992) Comparative studies on the serum cholesterol lowering action of whey protein and soybean protein in rats. Biosci Biotechnol Biochem 56:1484–1485CrossRefGoogle Scholar
  39. Nagaoka S, Miwa K, Eto M, Kuzuya Y, Hori G, Yamamoto K (1999) Soy protein peptic hydrolysate with bound phospholipids decreases micellar solubility and cholesterol absorption in rats and caco-2 cells. J Nutr 129:1725–1730PubMedGoogle Scholar
  40. Nagata C, Takatsuka N, Kurisu Y, Shimizu H (1998) Decreased serum total cholesterol concentration associated with high intake of soy products in Japanese men and women. J Nutr 128:209–213PubMedGoogle Scholar
  41. Ni W, Tsuda Y, Sakono M, Imaizumi K (1998) Dietary soy protein isolate, compared with casein, reduces atherosclerotic lesion area in apolipoprotein E-deficient mice. J Nutr 128:1884–1889PubMedGoogle Scholar
  42. Nissen S, Sharp RL, Panton L, Vukovitch M, Trappe S, Fuller JC (2000) Beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr 130:1937–1945PubMedGoogle Scholar
  43. Ohtani M, Maruyama K, Sugita M, Kobayashi K (2001) Amino acid supplementation affects hematological and biochemical parameters in elite rugby players. Biosci Biotechnol Biochem 65:1970–1976. doi: 10.1271/bbb.65.1970 CrossRefPubMedGoogle Scholar
  44. Potter SM (1995) Overview of proposed mechanisms for the hypercholesterolemic effect of soy. J Nutr 125:606S–611SPubMedGoogle Scholar
  45. Potter SM, Pertile J, Berber-Jimenez MD (1996) Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters. J Nutr 126:2007–2011PubMedGoogle Scholar
  46. Potter SM, Baum JA, Stillman RJ, Shay NF, Erdman JW (1998) Soy protein isiflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68:1375S–1379SPubMedGoogle Scholar
  47. Rabinowitz JL (1955) The biosynthesis of radioactive beta-hydroxyisovaleric acid in rat liver. J Am Chem Soc 77:1295–1297. doi: 10.1021/ja01610a069 CrossRefGoogle Scholar
  48. Rudney H (1957) The biosynthesis of beta-hydroxy-beta-methylglutaric acid. J Biol Chem 227:363–377PubMedGoogle Scholar
  49. Sabourin PJ, Bieber LL (1983) Formation of beta-hydroxyisovalerate by an alpha-ketoisocaproate oxygenase in human liver. Metabolism 32:160–164. doi: 10.1016/0026-0495(83)90223-8 CrossRefPubMedGoogle Scholar
  50. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M (2006) Soy protein, isoflavones, and cardiovascular health: an American Heart Association science advisory for professionals from the Nutrition Committee. Circulation 113:1034–1044. doi: 10.1161/CIRCULATIONAHA.106.171052 CrossRefPubMedGoogle Scholar
  51. Sérougne C, Férézou J, Rukaj A (1987) A new relatioship between cholesterolemia and cholesterol synthesis determined in rats fed an excess of cystine. Biochim Biophys Acta 921:522–530PubMedGoogle Scholar
  52. Sérougne C, Felgines C, Férézou J, Hajri T, Bertin C, Mazur A (1995) Hypertcholesterolemia induced by cholesterol- or cystine-enriched diet is characterized by different plasma lipoprotein and apolipoprotein concentrations in rats. J Nutr 125:35–41PubMedGoogle Scholar
  53. Shukla A, Bettzieche A, Hirche F, Brandsch C, Stangl GI, Eder K (2006) Dietary fish protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model. Br J Nutr 96:674–682PubMedGoogle Scholar
  54. Sirtori CR, Pazzucconi F, Colombo L, Battistin P, Bondioli A, Dezscheemaeker K (1999) Double blind study of the addition of high-protein soya milk vs. cow’s milk and resistance to or intolerance of statins. Br J Nutr 82:91–96PubMedGoogle Scholar
  55. Teixera SR, Potter SM, Weigel R, Hannum S, Erdman JW, Hasler CM (2000) Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderatly hypercholesterolemic men. Am J Clin Nutr 71:1077–1084Google Scholar
  56. Tomatoke H, Shimaoka I, Kayashita J, Yokoyama F, Nakajoh M, Kato N (2000) A buckwheat protein product suppresses gallstone formation and plasma cholesterol more strongly than soy protein isolate in hamsters. J Nutr 130:1670–1674Google Scholar
  57. Tonstad S, Smerud K, Hoie L (2002) A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects. Am J Clin Nutr 76:78–84PubMedGoogle Scholar
  58. US Food and Drug Administration (1999) Food labelling health claims: soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist 64:57700–57733Google Scholar
  59. Velez-Carrasco W, Merkel M, Twiss CO, Smith JD (2008) Dietary methionine effects on plasma homocysteine and HDL metabolism in mice. J Nutr Biochem 19:362–370. doi: 10.1016/j.jnutbio.2007.05.005 CrossRefPubMedGoogle Scholar
  60. Wang Y, Jones PJ, Ausman LM, Lichtenstein AH (2004) Soy protein reduces triglycerides levels and triglycerides fatty acid fractional synthesis rate in hypercholesterolemic subjects. Atherosclerosis 173:269–275. doi: 10.1016/j.atherosclerosis.2003.12.015 CrossRefPubMedGoogle Scholar
  61. Washburn S, Burke GL, Morgan T, Anthony M (1999) Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 6:7–13. doi: 10.1097/00042192-199906010-00004 CrossRefPubMedGoogle Scholar
  62. Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mork S, Berge RK (2004) Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. J Nutr 134:1320–1327PubMedGoogle Scholar
  63. West SG, Hilpert KF, Juturu V, Bordi PL, Lampe JW, Mousa SA, Kris-Etherton PM (2005) Effect of including soy protein in a blood cholesterol-lowering diet on markers of cardiac risk in men and in postmenopausal women with and without hormone replacement therapy. J Womens Health 14:353–362. doi: 10.1089/jwh.2005.14.253 CrossRefGoogle Scholar
  64. Wong WW, Smith EO, Stuff JE, Hachey DL, Heird WC, Pownell HJ (1998) Cholesterol-lowering effect of soy protein in normocholesterolemic and hypercholesterolemic men. Am J Clin Nutr 68:1385S–1389SPubMedGoogle Scholar
  65. Xiao CW (2008) Health effects of soy protein and isoflavones in humans. J Nutr 138:1244S–1249SPubMedGoogle Scholar
  66. Yamori Y, Murakami S, Ikeda K, Nara Y (2004) Fish and lifestyle-related disease prevention: experimental and epidemiological evidence for anti-atherogenic potential of taurine. Clin Exp Pharmacol Physiol 31:S20–S23. doi: 10.1111/j.1440-1681.2004.04122.x CrossRefPubMedGoogle Scholar
  67. Yanni AE, Perrea DN, Yatzidis HA (2005) Effects of antiatherogenic l-aspartate and l-glutamate on serum lipoproteins cholesterol and apolipoproteins A-1 and B in rabbits fed with high-cholesterol diet. Nutr Metab Cardiovasc Dis 15:161–165. doi: 10.1016/j.numecd.2004.06.001 CrossRefPubMedGoogle Scholar
  68. Yokogushi H, Oda H (2002) Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. Amino Acids 23:433–439. doi: 10.1007/s00726-002-0211-1 CrossRefGoogle Scholar
  69. Zabin I, Bloch K (1951) The utilization of butyric acid for the synthesis of cholesterol and fatty acids. J Biol Chem 192:261–266PubMedGoogle Scholar
  70. Zanchi NE, Nicastro H, Lancha AH (2008) Potential antiproteolytic effects of l-leucine: observations of in vitro and in vivo studies. Nutr Metab 5:20–26. doi: 10.1186/1743-7075-5-20 CrossRefGoogle Scholar
  71. Zhan S, Ho SC (2005) Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 81:397–408PubMedGoogle Scholar
  72. Zhang X, Beynen AC (1993) Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats. Br J Nutr 69:767–777. doi: 10.1079/BJN19930077 CrossRefPubMedGoogle Scholar
  73. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH (2007) Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56:1647–1654. doi: 10.2337/db07-0123 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • François Blachier
    • 1
  • Antonio H. LanchaJr
    • 2
  • Claire Boutry
    • 1
  • Daniel Tomé
    • 1
  1. 1.INRA, CNRH-IdF, AgroParisTech, UMR 914 Nutrition Physiology and Ingestive BehaviorParisFrance
  2. 2.Laboratory of Applied Nutrition and Metabolism, Physical Education and School of SportsUniversity of Sao PauloSao PauloBrazil

Personalised recommendations