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. 1982 May;69(5):1072–1080. doi: 10.1172/JCI110542

Effects of dietary cholesterol and fatty acids on plasma lipoproteins.

G Schonfeld, W Patsch, L L Rudel, C Nelson, M Epstein, R E Olson
PMCID: PMC370171  PMID: 7068846

Abstract

The effects of dietary cholesterol and fatty acids on low density and high density lipoproteins (LDL and HDL) were studied in 20 young men. After 2-3 wk of evaluations on ad lib. diets, basal diets, which consisted of 15% protein, 45% carbohydrates, 40% fat, and 300 mg/day of cholesterol, were given for 4-5 wk (Basal). The ratio of dietary polyunsaturated to saturated fatty acids (P/S) for different groups of subjects were 0.25, 0.4, 0.8, or 2.5. 750 and 1,500 mg/d of cholesterol were added to the basal diets as 3 and 6 eggs, respectively. Total cholesterol and LDL cholesterol were lower in all subjects on the basal diets than on the ad lib. diets. Addition of 750 mg cholesterol to the diet with P/S = 0.25-0.4 raised LDL cholesterol by 16 +/- 14 mg/dl to 115% of basal diet values (n = 11, P less than 0.01); 1,500 mg increased LDL cholesterol by 25 +/- 19 mg/dl to 125% (n = 9, P less than 0.01). On the diet with P/S = 0.8, 750 mg produced insignificant increases in LDL cholesterol, but 1,500 mg produced increases of 17 +/- 22 mg/dl to 115% of basal (n = 6, P less than 0.02). On the P/S = 2.5 diet, neither 750 nor 1,500 mg produced significant changes. Thus, both the cholesterol contents and P/S ratios of diets were important in determining LDL levels. The lipid and apoprotein compositions, flotation rates, molecular weights, and binding by cellular receptors of LDL were virtually unchanged by the addition of cholesterol to the diets high in saturated fat. These diets, therefore, caused an increase in the number of LDL particles of virtually unchanged physical and biological properties. On the diet with low P/S ratio, HDL2 rose, whereas this effect was absent on diets with high P/S ratios. The response of LDL to dietary manipulations is consonant with epidemiologic data relating diets high in cholesterol and saturated fat to atherogenesis. The response of HDL2, however, is opposite to that of its putative role as a negative risk factor. Further work is needed to clarify this interesting paradox.

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Selected References

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  1. AHRENS E. H., Jr, INSULL W., Jr, BLOMSTRAND R., HIRSCH J., TSALTAS T. T., PETERSON M. L. The influence of dietary fats on serum-lipid levels in man. Lancet. 1957 May 11;272(6976):943–953. doi: 10.1016/s0140-6736(57)91280-1. [DOI] [PubMed] [Google Scholar]
  2. Albers J. J., Cabana V. G., Warnick G. R., Hazzard W. R. Lp(a) lipoprotein: relationship to sinking pre-beta lipoprotein hyperlipoproteinemia, and apolipoprotein B. Metabolism. 1975 Sep;24(9):1047–1054. doi: 10.1016/0026-0495(75)90098-0. [DOI] [PubMed] [Google Scholar]
  3. Anderson J. T., Grande F., Keys A. Independence of the effects of cholesterol and degree of saturation of the fat in the diet on serum cholesterol in man. Am J Clin Nutr. 1976 Nov;29(11):1184–1189. doi: 10.1093/ajcn/29.11.1184. [DOI] [PubMed] [Google Scholar]
  4. Applebaum-Bowden D., Hazzard W. R., Cain J., Cheung M. C., Kushwaha R. S., Albers J. J. Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. Atherosclerosis. 1979 Aug;33(4):385–396. doi: 10.1016/0021-9150(79)90031-5. [DOI] [PubMed] [Google Scholar]
  5. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  6. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  7. Burslem J., Schonfeld G., Howald M. A., Weidman S. W., Miller J. P. Plasma apoprotein and lipoprotein lipid levels in vegetarians. Metabolism. 1978 Jun;27(6):711–719. doi: 10.1016/0026-0495(78)90009-4. [DOI] [PubMed] [Google Scholar]
  8. Castelli W. P., Doyle J. T., Gordon T., Hames C. G., Hjortland M. C., Hulley S. B., Kagan A., Zukel W. J. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation. 1977 May;55(5):767–772. doi: 10.1161/01.cir.55.5.767. [DOI] [PubMed] [Google Scholar]
  9. Cheung M. C., Albers J. J. The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay. J Clin Invest. 1977 Jul;60(1):43–50. doi: 10.1172/JCI108767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Connor W. E., Cerqueira M. T., Connor R. W., Wallace R. B., Malinow M. R., Casdorph H. R. The plasma lipids, lipoproteins, and diet of the Tarahumara indians of Mexico. Am J Clin Nutr. 1978 Jul;31(7):1131–1142. doi: 10.1093/ajcn/31.7.1131. [DOI] [PubMed] [Google Scholar]
  11. Connor W. E., Witiak D. T., Stone D. B., Armstrong M. L. Cholesterol balance and fecal neutral steroid and bile acid excretion in normal men fed dietary fats of different fatty acid composition. J Clin Invest. 1969 Aug;48(8):1363–1375. doi: 10.1172/JCI106102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dolphin P. J. Serum and hepatic nascent lipoproteins in normal and hypercholesterolemic rats. J Lipid Res. 1981 Aug;22(6):971–989. [PubMed] [Google Scholar]
  13. Falko J. M., Schonfeld G., Witztum J. L., Kolar J. B., Weidman S. W., Steelman R. Effects of diet on apoprotein E levels and on the apoprotein E subspecies in human plasma lipoproteins. J Clin Endocrinol Metab. 1980 Mar;50(3):521–528. doi: 10.1210/jcem-50-3-521. [DOI] [PubMed] [Google Scholar]
  14. Fisher W. R., Granade M. E., Mauldin J. L. Hydrodynamic studies of human low density lipoproteins. Evaluation of the diffusion coefficient and the preferential hydration. Biochemistry. 1971 Apr 27;10(9):1622–1629. doi: 10.1021/bi00785a019. [DOI] [PubMed] [Google Scholar]
  15. Flynn M. A., Nolph G. B., Flynn T. C., Kahrs R., Krause G. Effect of dietary egg on human serum cholesterol and triglycerides. Am J Clin Nutr. 1979 May;32(5):1051–1057. doi: 10.1093/ajcn/32.5.1051. [DOI] [PubMed] [Google Scholar]
  16. Goldstein J. L., Brown M. S. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed] [Google Scholar]
  17. Gonen B., Patsch W., Kuisk I., Schonfeld G. The effect of short-term feeding of a high carbohydrate diet on HLD subclasses in normal subjects. Metabolism. 1981 Nov;30(11):1125–1129. doi: 10.1016/0026-0495(81)90058-5. [DOI] [PubMed] [Google Scholar]
  18. Grundy S. M., Ahrens E. H., Jr The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man. J Clin Invest. 1970 Jun;49(6):1135–1152. doi: 10.1172/JCI106329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gustafson A., Lillienberg L., Svanborg A. Human plasma high-density lipoprotein composition during the menstrual cycle. Scand J Clin Lab Invest Suppl. 1974;137:63–70. [PubMed] [Google Scholar]
  20. KEYS A., ANDERSON J. T., MICKELSEN O., ADELSON S. F., FIDANZA F. Diet and serum cholesterol in man; lack of effect of dietary cholesterol. J Nutr. 1956 May 10;59(1):39–56. doi: 10.1093/jn/59.1.39. [DOI] [PubMed] [Google Scholar]
  21. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  22. Lin D. S., Connor W. E. The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion. J Lipid Res. 1980 Nov;21(8):1042–1052. [PubMed] [Google Scholar]
  23. Mahley R. W., Holcombe K. S. Alterations of the plasma lipoproteins and apoproteins following cholesterol feeding in the rat. J Lipid Res. 1977 May;18(3):314–324. [PubMed] [Google Scholar]
  24. Mahley R. W., Innerarity T. L., Bersot T. P., Lipson A., Margolis S. Alterations in human high-density lipoproteins, with or without increased plasma-cholesterol, induced by diets high in cholesterol. Lancet. 1978 Oct 14;2(8094):807–809. doi: 10.1016/s0140-6736(78)92588-6. [DOI] [PubMed] [Google Scholar]
  25. Mahley R. W., Innerarity T. L., Brown M. S., Ho Y. K., Goldstein J. L. Cholesteryl ester synthesis in macrophages: stimulation by beta-very low density lipoproteins from cholesterol-fed animals of several species. J Lipid Res. 1980 Nov;21(8):970–980. [PubMed] [Google Scholar]
  26. Mahley R. W., Innerarity T. L. Interaction of canine and swine lipoproteins with the low density lipoprotein receptor of fibroblasts as correlated with heparin/manganese precipitability. J Biol Chem. 1977 Jun 10;252(11):3980–3986. [PubMed] [Google Scholar]
  27. Mahley R. W., Innerarity T. L., Weisgraber K. H., Fry D. L. Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. Am J Pathol. 1977 Apr;87(1):205–226. [PMC free article] [PubMed] [Google Scholar]
  28. Mahley R. W., Weisgraber K. H., Innerarity T. Atherogenic hyperlipoproteinemia induced by cholesterol feeding the Patas monkey. Biochemistry. 1976 Jul 13;15(14):2979–2985. doi: 10.1021/bi00659a007. [DOI] [PubMed] [Google Scholar]
  29. Mahley R. W., Weisgraber K. H., Innerarity T. Canine lipoproteins and atherosclerosis. II. Characterization of the plasma lipoproteins associated with atherogenic and nonatherogenic hyperlipidemia. Circ Res. 1974 Nov;35(5):722–733. doi: 10.1161/01.res.35.5.722. [DOI] [PubMed] [Google Scholar]
  30. Mattson F. H., Erickson B. A., Kligman A. M. Effect of dietary cholesterol on serum cholesterol in man. Am J Clin Nutr. 1972 Jun;25(6):589–594. doi: 10.1093/ajcn/25.6.589. [DOI] [PubMed] [Google Scholar]
  31. Miller G. J. High density lipoproteins and atherosclerosis. Annu Rev Med. 1980;31:97–108. doi: 10.1146/annurev.me.31.020180.000525. [DOI] [PubMed] [Google Scholar]
  32. Mistry P., Miller N. E., Laker M., Hazzard W. R., Lewis B. Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man. Studies of low density lipoprotein receptor activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in blood mononuclear cells. J Clin Invest. 1981 Feb;67(2):493–502. doi: 10.1172/JCI110058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nestel P. J., Havenstein N., Whyte H. M., Scott T. J., Cook L. J. Lowering of plasma cholesterol and enhanced sterol excretion with the consumption of polyunsaturated ruminant fats. N Engl J Med. 1973 Feb 22;288(8):379–382. doi: 10.1056/NEJM197302222880801. [DOI] [PubMed] [Google Scholar]
  34. Nestel P. J., Poyser A. Changes in cholesterol synthesis and excretion when cholesterol intake is increased. Metabolism. 1976 Dec;25(12):1591–1599. doi: 10.1016/0026-0495(76)90112-8. [DOI] [PubMed] [Google Scholar]
  35. Nichols A. B., Ravenscroft C., Lamphiear D. E., Ostrander L. D., Jr Daily nutritional intake and serum lipid levels. The Tecumseh study. Am J Clin Nutr. 1976 Dec;29(12):1384–1392. doi: 10.1093/ajcn/29.12.1384. [DOI] [PubMed] [Google Scholar]
  36. Ostlund R. E., Jr, Pfleger B., Schonfeld G. Role of microtubules in low density lipoprotein processing by cultured cells. J Clin Invest. 1979 Jan;63(1):75–84. doi: 10.1172/JCI109281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Patsch J. R., Sailer S., Kostner G., Sandhofer F., Holasek A., Braunsteiner H. Separation of the main lipoprotein density classes from human plasma by rate-zonal ultracentrifugation. J Lipid Res. 1974 Jul;15(4):356–366. [PubMed] [Google Scholar]
  38. Patsch W., Schonfeld G., Gotto A. M., Jr, Patsch J. R. Characterization of human high density lipoproteins by zonal ultracentrifugation. J Biol Chem. 1980 Apr 10;255(7):3178–3185. [PubMed] [Google Scholar]
  39. Redgrave T. G., Snibson D. A. Clearance of chylomicron triacylglycerol and cholesteryl ester from the plasma of streptozotocin-induced diabetic and hypercholesterolemic hypothyroid rats. Metabolism. 1977 May;26(5):493–503. doi: 10.1016/0026-0495(77)90093-2. [DOI] [PubMed] [Google Scholar]
  40. Rudel L. L., Lee J. A., Morris M. D., Felts J. M. Characterization of plasma lipoproteins separated and purified by agarose-column chromatography. Biochem J. 1974 Apr;139(1):89–95. doi: 10.1042/bj1390089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rudel L. L., Pitts L. L., 2nd, Nelson C. A. Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol. J Lipid Res. 1977 Mar;18(2):211–222. [PubMed] [Google Scholar]
  42. Schonfeld G., Chen J., McDonnell W. F., Jeng I. Apolipoprotein A-II content of human plasma high density lipoproteins measured by radioimmunoassay. J Lipid Res. 1977 Sep;18(5):645–655. [PubMed] [Google Scholar]
  43. Schonfeld G., George P. K., Miller J., Reilly P., Witztum J. Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism. 1979 Oct;28(10):1001–1010. doi: 10.1016/0026-0495(79)90004-0. [DOI] [PubMed] [Google Scholar]
  44. Schonfeld G., Lees R. S., George P. K., Pfleger B. Assay of total plasma apolipoprotein B concentration in human subjects. J Clin Invest. 1974 May;53(5):1458–1467. doi: 10.1172/JCI107694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schonfeld G., Pfleger B. The structure of human high density lipoprotein and the levels of apolipoprotein A-I in plasma as determined by radioimmunoassay. J Clin Invest. 1974 Aug;54(2):236–246. doi: 10.1172/JCI107758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schonfeld G., Weidman S. W., Witztum J. L., Bowen R. M. Alterations in levels and interrelations of plasma apolipoproteins induced by diet. Metabolism. 1976 Mar;25(3):261–275. doi: 10.1016/0026-0495(76)90084-6. [DOI] [PubMed] [Google Scholar]
  47. Shekelle R. B., Shryock A. M., Paul O., Lepper M., Stamler J., Liu S., Raynor W. J., Jr Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. N Engl J Med. 1981 Jan 8;304(2):65–70. doi: 10.1056/NEJM198101083040201. [DOI] [PubMed] [Google Scholar]
  48. Shepherd J., Packard C. J., Grundy S. M., Yeshurun D., Gotto A. M., Jr, Taunton O. D. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res. 1980 Jan;21(1):91–99. [PubMed] [Google Scholar]
  49. Spritz N., Mishkel M. A. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids. J Clin Invest. 1969 Jan;48(1):78–86. doi: 10.1172/JCI105976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. St Clair R. W., Mitschelen J. J., Leight M. Metabolism by cells in culture of low-density lipoproteins of abnormal composition from non-human primates with diet-induced hypercholesterolemia. Biochim Biophys Acta. 1980 Apr 18;618(1):63–79. doi: 10.1016/0005-2760(80)90054-5. [DOI] [PubMed] [Google Scholar]
  51. Stein E. A., Mendelsohn D., Fleming M., Barnard G. D., Carter K. J., du Toit P. S., Hansen J. D., Bersohn I. Lowering of plasma cholesterol levels in free-living adolescent males; use of natural and synthetic polyunsaturated foods to provide balanced fat diets. Am J Clin Nutr. 1975 Nov;28(11):1204–1216. doi: 10.1093/ajcn/28.11.1204. [DOI] [PubMed] [Google Scholar]
  52. Swift L. L., Manowitz N. R., Dunn G. D., LeQuire V. S. Isolation and characterization of hepatic Golgi lipoproteins from hypercholesterolemic rats. J Clin Invest. 1980 Sep;66(3):415–425. doi: 10.1172/JCI109871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tan M. H., Dickinson M. A., Albers J. J., Havel R. J., Cheung M. C., Vigne J. L. The effect of a high cholesterol and saturated fat diet on serum high-density lipoprotein-cholesterol, apoprotein A-I, and apoprotein E levels in normolipidemic humans. Am J Clin Nutr. 1980 Dec;33(12):2559–2565. doi: 10.1093/ajcn/33.12.2559. [DOI] [PubMed] [Google Scholar]
  54. Wood P. D., Shioda R., Kinsell L. W. Dietary regulation of cholesterol metabolism. Lancet. 1966 Sep 17;2(7464):604–607. doi: 10.1016/s0140-6736(66)91924-6. [DOI] [PubMed] [Google Scholar]

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