Summary
Different dietary proteins determine different serum cholesterol levels if fed in a semisynthetic diet to some, but not all, animal species. In one species, the rabbit, this metabolic response is elicited without adding high sucrose or cholesterol supplements that have to be added to rat or pig diets in order to cause a similar response. Eleven out of 13 studies show that casein and soy protein do not induce different serum cholesterol levels in normal man. More important, protein-induced differences of serum cholesterol concentrations have not been reported when appropriate nutritional methodology has been applied. We conclude that no protein-induced hypercholesterolemia is observed in primates, particularly not in the human species. Dietary recommendations urging the general public to reduce consumption of animal protein because of a higher atherogenicity are not supported by the present data. The biochemical basis of the metabolic responses has been studied by many investigators, but no convincing unifying concept has yet been identified. The recent observation of higher serum thyroxine concentrations following soy protein consumption (and vegetable protein in general) when compared to casein shed new light on this problem. This endocrine response explains a wide array of metabolic features of soy-fed rodents: the lower hepatic VLDL secretion, the higher hepatic HMG-CoA reductase activity, the higher hepatic apo B, E receptor activity, the higher fecal bile acid excretion, and finally the lower serum cholesterol concentrations.
Similar content being viewed by others
Abbreviations
- HDL:
-
High density lipoprotein
- HMG-CoA reductase:
-
β-hyroxy-β-methyl-glutaryl
- CoA:
-
reductase (E.C.1.1.1.34)
- LDL:
-
Low density lipoprotein
- P/S ratio:
-
Polyunsaturated to saturated fatty acids
- VLDL:
-
Very low density lipoprotein
References
Agdeppa D, Macaron C, Mallik T, Schnuda ND (1979) Plasma high density lipoprotein cholesterol in thyroid disease. J Clin Endocrinol Metab 49:726–729
Anderson JT, Grande F, Keys A (1971) Effect on man's serum lipids of two proteins with different amino acid composition. Am J Clin Nutr 24:524–530
Apostolopoulos JJ, Howlett GJ, Fidge N (1987) Effects of dietary cholesterol and hypothyroidism on rat apolipoprotein mRNA metabolism. J Lipid Res 28:642–648
Asayama K, Amemiya S, Kusano S, Kato K (1984) Growth-hormone-induced changes in postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activity. Metabolism 33:129–131
Aubry F, Marcel YL, Davignon J (1974) Effects of glucagon on plasma lipids in different types of primary hyperlipoproteinemia. Metabolism 23:225–238
Barth CA, Pfeuffer M, Hahn G (1984) Influence of dietary casein or soy protein on serum lipids and lipoproteins of monkeys (Macaca fasciularis). Ann Nutr Metab 28:137–143
Bennion LJ, Grundy SM (1977) Effects of diabetes mellitus on cholesterol metabolism in man. N Engl J Med 296:1365–1371
Bodwell CE, Schuster EM, Steele PS (1980) Effects of dietary soy protein on plasma lipid profiles of adult men. Fed Proc 39:1113
Briones ER, Mao SJT, Palumbo PJ, O'Fallon WM, et al. (1984) Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics. Metabolism 33:42–49
Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212:628–635
Byers SO, Friedman M, Rosenman RH (1970) Prevention of Hypercholesterolemia in thyroidectomized rats by growth hormone. Nature 228:464–465
Calvert GD, Blight L, Illman RJ et al. (1981) A trial of the effects of soya-bean flour and soya-bean saponins on plasma lipids, faecal bile acids and neutral sterols in hypercholesterolaemic men. Br J Nutr 45:277–281
Campbell AM, Swendseid ME, Griffith WH, Tuttle WG (1965) Serum lipids of men fed diets differing in protein quality and linoleic acid content. Am J Clin Nutr 17:83
Carroll KK (1982) Hypercholesterolemia and atherosclerosis: effects of dietary protein. Fed Proc 41:2792–2796
Carroll KK, Hamilton RMG (1975) Effects of dietary protein and carbohydrate on plasma cholesterol levels in relation to atherosclerosis. J Food Sci 40:18–23
Carroll KK, Giovannetti PM, Huff MW et al. (1978) Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women. Am J Clin Nutr 31:1312–1321
Cho BHS, Egwim PO, Fahey GC (1985) Plasma lipid and lipoprotein cholesterol levels in swine. Modification of protein-induced response by added cholesterol and soy fiber. Atherosclerosis 56:39–49
Cohn JS, Nestel PJ (1985) Hepatic lipoprotein receptor activity in rats fed casein and soy protein. Atherosclerosis 56:247–250
Connor WE, Connor SL (1972) The key role of nutritional factors on the prevention of coronary heart disease. Prev Med 1:49–83
Cree TC, Schalch DS (1985) Protein utilization in growth: effect of lysine deficiency on serum growth hormone, somatomedins, insulin, total thyroxine (T4) and triiodothyronine, free T4 index, and total corticosterone. Endocrinology 117:667–673
Descovitch C, Gaddi A, Mannino G et al. (1980) Multicentre study of soybean protein diet for outpatient hypercholesterolaemic patients. Lancet II:709–712
Dugan RE, Ness GC, Lakshman MR, et al. (1974) Regulation of β-hydroxy-β-methylglutaryl-coenzyme A-reductase by the interplay of hormones. Arch Biochem Biophys 161:499–504
Forsythe WA (1986) Comparison of dietary casein or soy protein effects on plasma lipids and hormone concentrations in the gerbil (Meriones unguiculatus). J Nutr 116:1165–1171
Friedman M, Byers SO, Rosenman RH (1952) Changes in excretion of intestinal cholesterol and sterol digitonides in hyper- and hypothyroidism. Circulation 5:657–660
Friedman M, Byers SO, Elek SR (1970) Pituitary growth hormone essential for regulation of serum cholesterol. Nature 225:464–467
Fumagalli R, Soleri L, Farina R et al. (1982) Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet. Atherosclerosis 43:341–353
Goldberg AP, Lim A, Kolar JB et al. (1982) Soybean protein independently lowers plasma cholesterol levels in primary hypercholesterolemia. Atherosclerosis 43:355–368
Grundy SM, Abrams JJ (1983) Comparison of actions of soy protein and casein on metabolism of plasma lipoproteins and cholesterol in humans. Am J Clin Nutr 38:245–252
Guder W, Nolte I, Wieland O (1968) The influence of thyroid hormones on β-hydroxy-β-methylglutaryl coenzyme A reductase of rat liver. Eur J Biochem 4:273–278
Hagemeister H, Scholz-Ahrens K-E, Barth CA (1987) Influence of casein and soy protein on plasma amino acids in the miniature pig. (unpublished)
Hansson P, Valdemarsson S, Nilsson-Ehle P (1983) Experimental hyperthyroidism in man: effects on plasma lipoproteins, lipoprotein lipase and hepatic lipase. Horm Metabol Res 15:449–452
Helms P (1977) Soybean-protein diet and plasma-cholesterol. Lancet I:805
Henze K, Seidl O, Wolfram G, Zöllner N (1981) Der Einfluß einer Therapie mit Kortikosteroiden auf die Serumlipide. Verh Dtsch Ges Inn Med 87:982–984
Heubi JE, Burstein S, Sperling MA et al. (1983) The role of human growth hormone in the regulation of cholesterol and bile acid metabolism. J Clin Endocrinol Metab 57:885–891
Hevia P, Clary RA, Visek WJ (1979) Serum and liver lipids in rats fed casein or soybean protein with sucrose or dextrin or sucrose and cholesterol. Nutr Rep Int 20:539–548
Hillmar I, Barth CA (1979) Einfluß von Hormonen auf die β-Hydroxy-β-methylglutaryl-CoA Reduktase in Leberzellkulturen. Hoppe-Seyler's Zschr Physiol Chem 360:283
Holmes WL, Rubel GB, Hood SS (1980) Comparison of the effect of dietary meat versus dietary soybean protein on plasma lipids of hyperlipidemic individuals. Atherosclerosis 36:379–387
Huff MW, Carroll KK (1980) Effects of dietary proteins on turnover, oxidation and absorption of cholesterol and on steroid excretion in rabbits. J Lipid Res 21:546–558
Huff MW, Giovanetti PM, Wolfe BM (1984) Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men. Am J Clin Nutr 39:888–897
Ignatowski A (1909) Über die Wirkung des tierischen Eiweisses auf die Aorta und die parenchymatösen Organe der Kaninchen. Virchows Arch A 198:248–270
Kannel WB, Castelli WP, Gordon T (1979) Cholesterol in the prediction of atherosclerosis disease. New perspectives bases on the Framingham study. Ann Intern Med 90:85–91
Keyes WG, Heimberg M (1979) Influence of thyroid status on lipid metabolism in the perfused liver. J Clin Invest 64:182–190
Kritchevsky D (1979) Vegetable protein and atherosclerosis. J Am Oil Chem Soc 56:135–140
Kritchevsky D, Tepper SA, Williams DE, Story WA (1977) Experimental atherosclerosis in rabbits fed cholesterol-free diets. 7. Interaction of animal or vegetable protein with fiber. Atherosclerosis 26:397–403
Lembke A, Greggersen H, Kay H et al. (1981) Zur Frage der atherogenen Wirkung von Casein. Milchwissenschaft 36:557–561
Lembke A, Greggersen H, Kay H et al. (1983) Comparative studies on atherogenic effects of soy protein and casein. Milchwissenschaft 38:538–541
Lovati MR, Allievi L, Sirtori CR (1985) Accelerated early catabolism of very low density lipoproteins in rats after dietary soy proteins. Atherosclerosis 56:243–246
Lopes-Virella ME, Wohltmann HJ, Loadholt CB, Buse MG (1981) Plasma lipids and lipoproteins in young insulin-dependent diabetic patients: Relationship with control. Diabetologia 21:216–223
Meinertz H, Nilansen K, Faergeman O (1984) Effect of dietary soy protein and casein on plasma lipoproteins in normolipidemic subjects. Circulation (Suppl II) 70:11–209
Mercer NJH, Carroll KK, Giovanetti PM et al. (1987) Effects on human plasma lipids of substituting soybean protein isolate for milk protein in the diet. Nutr Rep Int 35:279–287
Nagata Y, Imaizumi K, Sugano M (1980) Effects of soy bean protein and casein on serum cholesterol levels in rats. Br J Nutr 44:113–121
Pfeuffer M, Barth CA (1986) Modulation of very low density lipoprotein secretion by dietary protein is age-dependent in rats. Ann Nutr Metab 30:281–288
Pfeuffer M, Barth CA (1988) Influence of casein versus soy protein on lipid metabolism in minipigs. Ann Nutr Metab (in press)
Raaij JMA van, Katan MB, Hautvast JGAJ (1979) Casein, soya protein, serum cholesterol. Lancet II:958
Raaij JMA van, Katan MB, Hautvast JGAJ et al. (1981) Effects of casein versus soy protein diets on serum cholesterol and lipoproteins in young healthy volunteers. Am J Clin Nutr 34:1261–1271
Raaij JMA van, Katan MB, West CE, Hautvast JAGJ (1982) Influence of diets containing casein, soy isolate and soy concentrate on serum cholesterol and lipoproteins in middle-aged volunteers. Am J Clin Nutr 35:925–934
Reiser R, Henderson GR, O'Brien BC, Thomas J (1977) Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase of rats fed semipurified and stock diets. J Nutr 107:453–457
Roberts DCK, Stalmach ME, Khalil MW et al. (1981) Effects of dietary protein on composition and turnover of apoproteins in plasma lipoproteins of rabbits. Can J Biochem 59:642–647
Sacks FM, Breslow JL, Wood DG, Kass EH (1983) Lack of an effect of dairy protein (casein) and soy protein on plasma cholesterol of strict vegetarians. An experiment and a critical review. J Lipid Res 24:1012–1020
Sadur CN, Eckel RH (1983) Insulin-mediated increases in the HDL cholesterol/cholesterol ratio in humans. Arteriosclerosis 3:339–343
Sautier C, Doucet C, Flament C, Lemonnier D (1979) Effects of soy protein and saponins on serum, tissue and feces steroids in rat. Atherosclerosis 34:233–241
Schneeman BO, Gallaher D (1980) Changes in small intestinal digestive enzyme activity and bile acids with dietary cellulose in rats. J Nutr 110:584–590
Scholz K-E, Kinder E, Hagemeister H, Barth CA (1985) Influence of dietary casein and soy protein isolate on intestinal cholesterol and bile acid concentration. Z Ernährungswiss 24:158–171
Scholz-Ahrens K-E, Hagemeister H, Barth CA (1987) Influence of soy protein or casein on plasma hormone concentrations in pigs. (unpublished observations)
Schwandt P, Richter WO, Weisweiler P (1981) Soybean protein and serum cholesterol. Atherosclerosis 40:371–372
Shorey RAL, Bazan B, Lo GS (1981) Determinants of hypocholesterolemic response to soy and animal protein-based diets. Am J Clin Nutr 34:1769–1778
Sirtori CR, Agardi E, Conti F et al. (1977) Soybean-protein diet in the treatment of type-II hyperlipoproteinaemia. Lancet I:275–277
Sirtori CR, Galli G, Lovati MR et al. (1984) Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats. J Nutr 114:1493–1500
Stratum P van, Rudrum H, ten Hoor F et al. (1978) Physiologische Aspekte einer menschlichen Ernährung mit sojaproteinhaltigen Produkten. In: Harmer R, et al. (eds) Probleme um neue Lebensmittel. W. Mandrich, Wien, pp 247–261
Sugano M, Tanaka K, Ide T (1982) Secretion of cholesterol, triglyceride and apoprotein AI by isolated perfused liver from rats fed soybean protein and casein or their amino acid mixtures. J Nutr 112:855–862
Terpstra AHM, van Tintelen G, West CE (1982) The effect of semipurified diets containing different proportions of either casein or soybean protein on the concentration of cholesterol in whole serum, serum lipoproteins and liver in male and female rats. Atherosclerosis 42:85–95
Terpstra AHM, Hermus RJJ, West CE (1983) The role of dietary protein in cholesterol metabolism. World Rev Nutr Diet 42:1–55
Terpstra AHM, West CE, Fennis JTCM (1984) Hypercholesterolemic effect of dietary soy protein versus casein in rhesus monkeys (Macaca mulatta). Am J Clin Nutr 39:1–7
Troxler R, Sprague EA, Albanese RA, Fuchs R, Thompson AJ (1977) The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography. Atherosclerosis 26:151–162
Van der Meer R, de Vries HT (1985) Differential binding of glycine- and taurine-conjugated bile acids to insoluble calcium phosphate. Biochem J 229:265–268
Verillo A, de Teresa A, Carandente Giarusso P, La Rocca S (1985) Soybean protein diets in the management of type II hyperlipoproteinemia. Atherosclerosis 54:321–331
Vessby B, Karlström B, Lithell H et al. (1982) The effects on lipid and carbohydrate metabolism of replacing some animal protein by soy-protein in a lipid-lowering diet for hypercholesterolemic patients. Hum Nutr Appl Nutr 36A:179–189
Walker GR, Morse EH, Overley V (1972) The effect of animal protein and vegetable protein diets having the same fat content on the serum lipid levels of young women. J Nutr 72:317–321
West CE, Deuring K, Schutte JB, Terpstra AHM (1982) The effect of age on the development of hypercholesterolemia in rabbits fed semipurified diets containing casein. J Nutr 112:1287–1295
West CE, Beynen AC, Terpstra AHM, Scholz KE, Carroll KK, Woodward CJH (1983) The nature of dietary protein and serum cholesterol. Atherosclerosis 46:253–256
Wolfe BM, Giovanetti PM (1985) Elevation of VLDL-cholesterol during substitution of soy protein for animal protein in diets of hypercholesterolemic Canadians. Nutr Rep Int 32:1057–1065
Wolfe BM, Giovanetti PM, Cheng DCH et al. (1981) Hypolipidemic effect of substituting soybean protein isolate for all meat and dairy protein in the diets of hypercholesterolemic men. Nutr Rep Int 24:1187–1198
Author information
Authors and Affiliations
Additional information
This review is dedicated to Professor Nepomuk Zöllner on the occassion of his 65th birthday
Supported by the European Community (Grant 282/84-26.1)
Rights and permissions
About this article
Cite this article
Barth, C.A., Pfeuffer, M. Dietary protein and atherogenesis. Klin Wochenschr 66, 135–143 (1988). https://doi.org/10.1007/BF01727781
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01727781