Skip to main content

Does Dietary Cholesterol Matter?

Abstract

An ongoing dispute in the nutrition field is whether dietary cholesterol contributes significantly to elevated serum cholesterol and to atherosclerotic disease. Carefully controlled metabolic studies have shown that high-cholesterol intakes cause moderate increases in serum cholesterol levels. It is been difficult to verify this in population studies because of confounding factors. Nonetheless, meta-analysis of controlled studies documents a cholesterol-raising action of dietary cholesterol. Most of this effect occurs in low-density lipoproteins (LDLs), but the cholesterol content of other lipoproteins can be increased as well. Moreover, population studies strongly suggest that dietary cholesterol is atherogenic beyond any rise in LDL concentrations. It must be emphasized that dietary cholesterol is only one of several dietary factors influencing serum cholesterol levels. Others include saturated fatty acids, trans fatty acids, soluble fiber, and total caloric intake. To achieve substantial serum cholesterol lowering, favorable changes in all of these factors must be combined. To maximize cardiovascular risk reduction, a lifetime of a healthy diet is needed. Reduced cholesterol intake is only one of several factors required to achieve such a diet. In addition, reduction of cholesterol absorption can enhance serum cholesterol lowering. This can be attained by the addition of plant sterols or plant stanols to the diet or by use of ezetimibe, a cholesterol absorption blocker. By combining dietary cholesterol reduction with other cholesterol-lowering modalities, it should be possible to substantially reduce atherosclerosis throughout life short of using cholesterol-lowering drugs that act systemically.

This is a preview of subscription content, access via your institution.

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Anitschkow N, Chalatow S, Pelias MZ. Classics in arteriosclerosis research: on experimental cholesterin steatosis and its significance in the origin of some pathological processes. Arteriosclerosis. 1983;3:178–82.

    Article  Google Scholar 

  2. Clarkson TB. Animal models of atherosclerosis. Adv Vet Sci Comp Med. 1972;16:151–73.

    CAS  PubMed  Google Scholar 

  3. Kritchevsky D. Laboratory models for atherosclerosis. Adv Drug Res. 1974;9:41–53.

    CAS  PubMed  Google Scholar 

  4. Ritskes-Hoitinga J, Beynen AC. Atherosclerosis in the rat. Artery. 1988;16:25–50.

    CAS  PubMed  Google Scholar 

  5. Steinberg D. In celebration of the 100th anniversary of the lipid hypothesis of atherosclerosis. J Lipid Res. 2013;54:2946–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McNamara DJ. The fifty year rehabilitation of the egg. Nutrients. 2015;7:8716–22.

    Article  PubMed  PubMed Central  Google Scholar 

  7. McNamara DJ. Dietary cholesterol, heart disease risk and cognitive dissonance. Proc Nutr Soc. 2014;73:161–6.

    Article  CAS  PubMed  Google Scholar 

  8. Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet: II. The effect of cholesterol in the diet. Metabolism. 1965;14:759–65.

    Article  CAS  PubMed  Google Scholar 

  9. Hegsted DM, McGandy RB, Myers ML, Stare FJ. Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr. 1965;17:281–95.

    CAS  PubMed  Google Scholar 

  10. Hegsted DM. Serum-cholesterol response to dietary cholesterol: a re-evaluation. Am J Clin Nutr. 1986;44:299–305.

    CAS  PubMed  Google Scholar 

  11. Mattson FH, Erickson BA, Kligman AM. Effect of dietary cholesterol on serum cholesterol in man. Am J Clin Nutr. 1972;25:589–94.

    CAS  PubMed  Google Scholar 

  12. Hopkins PN. Effects of dietary cholesterol on serum cholesterol: a meta-analysis and review. Am J Clin Nutr. 1992;55:1060–70.

    CAS  PubMed  Google Scholar 

  13. •• Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ. Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr. 2015;102:276–94. Meta-analysis of 17 trials showed that high intakes of dietary cholesterol raises total serum cholesterol by about 5%.

    Article  CAS  PubMed  Google Scholar 

  14. Katan MB, Beynen AC. Characteristics of human hypo- and hyperresponders to dietary cholesterol. Am J Epidemiol. 1987;125:387–99.

    CAS  PubMed  Google Scholar 

  15. Beynen AC, Katan MB. Reproducibility of the variations between humans in the response of serum cholesterol to cessation of egg consumption. Atherosclerosis. 1985;57:19–31.

    Article  CAS  PubMed  Google Scholar 

  16. Katan MB, Berns MA, Glatz JF, Knuiman JT, Nobels A, de Vries JH. Congruence of individual responsiveness to dietary cholesterol and to saturated fat in humans. J Lipid Res. 1988;29:883–92.

    CAS  PubMed  Google Scholar 

  17. •• Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003;290:502–10. This study showed that multiple dietary changes, including reducing dietary cholesterol, can reduce serum LDL-cholesterol by 25-30%.

    Article  CAS  PubMed  Google Scholar 

  18. Crouse JR, Grundy SM. Evaluation of a continuous isotope feeding method for measurement of cholesterol absorption in man. J Lipid Res. 1978;19:967–71.

    CAS  PubMed  Google Scholar 

  19. Sudhop T, Reber M, Tribble D, et al. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. J Lipid Res. 2009;50:2117–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Grundy SM, Ahrens Jr EH, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res. 1969;10:304–15.

    CAS  PubMed  Google Scholar 

  21. Grundy SM, Ahrens Jr EH. Measurements of cholesterol turnover, synthesis, and absorption in man, carried out by isotope kinetic and sterol balance methods. J Lipid Res. 1969;10:91–107.

    CAS  PubMed  Google Scholar 

  22. Quintão E, Grundy SM, Ahrens Jr EH. An evaluation of four methods for measuring cholesterol absorption by the intestine in man. J Lipid Res. 1971;12:221–32.

    PubMed  Google Scholar 

  23. Quintão E, Grundy SM, Ahrens Jr EH. Effects of dietary cholesterol on the regulation of total body cholesterol in man. J Lipid Res. 1971;12:233–47.

    PubMed  Google Scholar 

  24. Sedaghat A, Samuel P, Crouse JR, Ahrens Jr EH. Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man. J Clin Invest. 1975;55:12–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Samuel P, Crouse JR, Ahrens Jr EH. Evaluation of an isotope ratio method for measurement of cholesterol absorption in man. J Lipid Res. 1978;19:82–93.

    CAS  PubMed  Google Scholar 

  26. McNamara DJ, Kolb R, Parker TS, et al. Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity. J Clin Invest. 1987;79:1729–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Samuel P, McNamara DJ, Ahrens Jr EH, Crouse JR, Parker T. Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man. J Lipid Res. 1982;23:480–9.

    CAS  PubMed  Google Scholar 

  28. Grundy SM, Mok HY. Determination of cholesterol absorption in man by intestinal perfusion. J Lipid Res. 1977;18:263–71.

    CAS  PubMed  Google Scholar 

  29. •• Altmann SW, Davis Jr HR, Zhu LJ, et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303:1201–4. This study demonstrated that intestinal protein NPC1L1 mediates cholesterol absorption.

    Article  CAS  PubMed  Google Scholar 

  30. Davis Jr HR, Zhu LJ, Hoos LM, et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem. 2004;279:33586–92.

    Article  CAS  PubMed  Google Scholar 

  31. Cohen JC, Pertsemlidis A, Fahmi S, et al. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci U S A. 2006;103(103):1810–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Grundy SM, Metzger AL. A physiological method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology. 1972;62:1200–17.

    CAS  PubMed  Google Scholar 

  33. Havel RJ. Postprandial hyperlipidemia and remnant lipoproteins. Curr Opin Lipidol. 1994;5:102–9.

    Article  CAS  PubMed  Google Scholar 

  34. Hanson J. John Cornforth (1917–2013). Nature. 2014;506:35.

    Article  CAS  PubMed  Google Scholar 

  35. Sharpe LJ, Brown AJ. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J Biol Chem. 2013;288:18707–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gould RG, Taylor CB, Hagerma JS, Warner I, Campbell DJ. Cholesterol metabolism. I. Effect of dietary cholesterol on the synthesis of cholesterol in dog tissue in vitro. J Biol Chem. 1953;201:519–28.

    CAS  PubMed  Google Scholar 

  37. Dietschy JM, Turley SD, Spady DK. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res. 1993;34:1637–59.

    CAS  PubMed  Google Scholar 

  38. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343:425–30.

    Article  CAS  PubMed  Google Scholar 

  39. Shimomura I, Bashmakov Y, Shimano H, Horton JD, Goldstein JL, Brown MS. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver. Proc Natl Acad Sci U S A. 1997;94:12354–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pertsemlidis D, Kirchman EH, Ahrens Jr EH. Regulation of cholesterol metabolism in the dog. I. Effects of complete bile diversion and of cholesterol feeding on absorption, synthesis, accumulation, and excretion rates measured during life. J Clin Invest. 1973;52:2353–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dietschy JM, Wilson JD. Regulation of cholesterol metabolism. 3. N Engl J Med. 1970;282:1241–9.

    Article  CAS  PubMed  Google Scholar 

  42. Cohen BI, Matoba N, Mosbach EH, McSherry CK. Dietary induction of cholesterol gallstones in hamsters from three different sources. Lipids. 1989;24:151–6.

    Article  CAS  PubMed  Google Scholar 

  43. Parks JS, Wilson MD, Johnson FL, Rudel LL. Fish oil decreases hepatic cholesteryl ester secretion but not apoB secretion in African green monkeys. J Lipid Res. 1989;30:1535–44.

    CAS  PubMed  Google Scholar 

  44. Huettinger M, Corbett JR, Schneider WJ, Willerson JT, Brown MS, Goldstein JL. Imaging of hepatic low density lipoprotein receptors by radionuclide scintiscanning in vivo. Proc Natl Acad Sci U S A. 1984;81:7599–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dietschy JM, Woollett LA, Spady DK. The interaction of dietary cholesterol and specific fatty acids in the regulation of LDL receptor activity and plasma LDL-cholesterol concentrations. Ann N Y Acad Sci. 1993;676:11–26.

    Article  CAS  PubMed  Google Scholar 

  46. Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. •• Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. This meta-analysis shows that for every 1% change in LDL-Cholesterol levels, there is an approximate 1% change in risk for cardiovascular disease over 5 years.

  48. •• Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60:2631–9. This study showed that for every 1% change in LDL-cholesterol over a lifetime the risk for atherosclerotic cardiovascular disease is changed by approximately 3%.

    Article  CAS  PubMed  Google Scholar 

  49. Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation. 1979;60:473–85.

    Article  CAS  PubMed  Google Scholar 

  50. Proctor SD, Vine DF, Mamo JC. Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis. Curr Opin Lipidol. 2002;13:461–70.

    Article  CAS  PubMed  Google Scholar 

  51. Proctor SD, Mamo JC. Intimal retention of cholesterol derived from apolipoprotein B100- and apolipoprotein B48-containing lipoproteins in carotid arteries of Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 2003;23:1595–600.

    Article  CAS  PubMed  Google Scholar 

  52. Tall AR, Small DM, Atkinson D, Rudel LL. Studies on the structure of low density lipoproteins isolated from Macaca fascicularis fed an atherogenic diet. J Clin Invest. 1978;62:1354–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mahley RW, Innerarity TL, Brown MS, Ho YK, Goldstein JL. Cholesteryl ester synthesis in macrophages: stimulation by beta-very low density lipoproteins from cholesterol-fed animals of several species. J Lipid Res. 1980;21:970–80.

    CAS  PubMed  Google Scholar 

  54. Castro GR, Fielding CJ. Effects of postprandial lipemia on plasma cholesterol metabolism. J Clin Invest. 1985;75:874–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Beynen AC, Katan MB. Effect of egg yolk feeding on the concentration and composition of serum lipoproteins in man. Atherosclerosis. 1985;54:157–66.

    Article  CAS  PubMed  Google Scholar 

  56. Weggemans RM, Zock PL, Katan MB. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis. Am J Clin Nutr. 2001;73:885–91.

    CAS  PubMed  Google Scholar 

  57. Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet. 1989;1:1177–9.

    Article  CAS  PubMed  Google Scholar 

  58. Katan MB, Grundy SM. Jones P, Law M, Miettinen T, Paoletti R; Stresa Workshop Participants. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003;78:965–78.

    Article  CAS  PubMed  Google Scholar 

  59. Garcia-Calvo M, Lisnock J, Bull HG, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005;102:8132–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sudhop T, Lütjohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106:1943–8.

    Article  CAS  PubMed  Google Scholar 

  61. Dujovne CA, Ettinger MP, McNeer JF, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1092–7. Erratum in: Am J Cardiol. 2003;91:1399.

    Article  CAS  PubMed  Google Scholar 

  62. •• Myocardial Infarction Genetics Consortium Investigators, Stitziel NO, Won HH, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371:2072–82. This study demonstrated that inactiving mutations of NPC1L reduces risk for coronary heart disease by approximately 46%.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Scott M. Grundy.

Ethics declarations

Conflict of Interest

Scott M. Grundy declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Nutrition

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Grundy, S.M. Does Dietary Cholesterol Matter?. Curr Atheroscler Rep 18, 68 (2016). https://doi.org/10.1007/s11883-016-0615-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-016-0615-0

Keywords

  • Dietary cholesterol
  • Cholesterol absorption
  • Eggs
  • Low-density lipoproteins
  • Plant sterols
  • Plant stanols
  • Ezetimibe