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The role of casein in the development of hypercholesterolemia

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Abstract

Atherosclerosis remains the leading cause of severe cardiovascular complications such as cardio- and cerebrovascular events. Given that prevention and early intervention play important roles in the reduction of cardiovascular complications associated with atherosclerosis, it is critical to better understand how to target the modifiable risk factors, such as diet, in order to best minimize their contributions to the development of the disease. Studies have shown that various dietary sources of protein can affect blood lipid levels, a modifiable risk factor for atherosclerosis, either positively or negatively. This clearly highlights that not all proteins are “created equal.” For example, consumption of diets high in either animal- or vegetable-based sources of protein have resulted in varied and inconsistent effects on blood cholesterol levels, often depending on the amino acid composition of the protein and the species investigated. Careful consideration of the source of dietary protein may play an important role in the prevention of atherosclerosis and subsequent cardiovascular complications. Given the recent focus on high protein diets, an emphasis on controlled studies in the area is warranted. The goal of this review is to present the current state of the literature that examines the effects of casein, a commonly utilized animal-based protein, on blood cholesterol levels and the varying effects noted in both animals and humans.

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References

  1. Anderson TJ (1999) Assessment and treatment of endothelial dysfunction in coronary artery disease and implications for therapy. J Am Coll Cardiol 34:631–638

    Article  CAS  PubMed  Google Scholar 

  2. Anderson JW, Fuller J, Patterson K, Blair R, Tabor A (2006) Soy compared to casein meal replacement shakes with high energy-restricted diets for obese women: randomized controlled trial. Metabolism 56:280–288

    Article  Google Scholar 

  3. Anthony MS, Clarkson TB, Bullock BC, Wagner JD (1997) Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler Thromb Vasc Biol 17:2524–2531

    Article  CAS  PubMed  Google Scholar 

  4. Antonio J, Incledon T (2001) The anticatabolics. In: Antonio J, Stout J (eds) Sports supplements. Lipincott Williams & Wilkins, Philadelphia, pp 111–136

    Google Scholar 

  5. Bendtsen LQ, Lorenzen JK, Bendsen NT, Rasmussen C, Astrup A (2013) Effect of dairy proteins on appetite, energy expenditure, body weight, and composition: a review of the evidence from controlled clinical trials. Adv Nutr 4(4):418–438

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Boirie YM, Dangin P, Gachon P, Vasson MP, Maubois JL, Beaufrere B (1997) Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A 94(26):14930–14935

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction—a marker for atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  CAS  PubMed  Google Scholar 

  8. Burges JW, Sinclair PA, Chretien CM, Boucher J, Sparks DL (2006) Reverse cholesterol transport. In: Cheema SK (ed) Biochemistry of atherosclerosis. Springer, New York, pp 3–22

    Chapter  Google Scholar 

  9. Campbell B (2012) Dietary protein efficiency: dietary protein types. In: Lowery LM, Antonio J (eds) Dietary protein and resistance exercise. CRC, Boca Raton, pp 95–114

    Chapter  Google Scholar 

  10. Carroll KK (1991) Review of clinical studies on cholesterol-lowering response to soy protein. J Am Diet Assoc 91(7):820–827

    CAS  PubMed  Google Scholar 

  11. Carroll KK, Kurowska EM (1995) Soy consumption and cholesterol reduction: review of animal and human studies. J Nutr 125:594S–597S

    CAS  PubMed  Google Scholar 

  12. Chao YS, Yasmin TT, Alberts AW (1982) Effects of cholestyramine on low density lipoprotein binding sites on liver membranes from rabbits with endogenous hypercholesterolemia induced by a wheat starch-casein diet. J Biol Chem 257:3623–3627

    CAS  PubMed  Google Scholar 

  13. Claessens M, Van Baak MA, Monsheimer S, Saris WHM (2009) The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors. Int J Obes 33:296–304

    Article  CAS  Google Scholar 

  14. Crouse JR, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL (1999) 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 Intern Med 159:2070–2076

    Article  CAS  PubMed  Google Scholar 

  15. Cullen P, Rauterberg J, Lorkowski S (2005) The pathogenesis of atherosclerosis. In: Von Eckardstein A (ed) Atherosclerosis: diet and drugs. Springer, New York, pp 3–70

    Google Scholar 

  16. Dangin M, Guillet C, Garcia-Rodenas C, Gachon P, Bouteloup-Demange C, Reiffers-Magnani K, Fauquant J, Ballevre O (2003) The rate of protein digestion affects protein gain differently during aging in humans. J Physiol 549(2):635–644

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Davies MJ (1997) The composition of coronary-artery plaques. N Engl J Med 336(18):1312–1314

    Article  CAS  PubMed  Google Scholar 

  18. Demling RH, DeSanti L (2000) Effects of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann Nutr Metab 44(1):21–29

    Article  CAS  PubMed  Google Scholar 

  19. Filios LC, Naito C, Andrus SB, Portman OW, Martin RS (1958) Variations in cardiovascular sudanophilia with changes in the dietary level of protein. Am J Physiol 194:275–279

    Google Scholar 

  20. Forrester JS (2008) The pathogenesis of atherosclerosis and plaque instability. In: Holtzman JL (ed) Atherosclerosis and oxidant stress. Springer, New York, pp 1–10

    Chapter  Google Scholar 

  21. Gross MD (2008) Lipids, oxidation, and cardiovascular disease. In: Holtzman JL (ed) Atherosclerosis and oxidant stress. Springer, New York, pp 79–96

    Chapter  Google Scholar 

  22. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695

    Article  CAS  PubMed  Google Scholar 

  23. Hermus RJJ, West CJ, Van Weerden EJ (1983) Failure of dietary-casein-induced acidosis to explain the hypercholesterolaemia of casein-fed rabbits. J Nutr 113(3):618–629

    CAS  PubMed  Google Scholar 

  24. Hu FB, Stampfer MJ, Manson JE et al (1999) Dietary protein and risk of ischemic heart disease in women. Am J Clin Nutr 70:221–227

    PubMed  Google Scholar 

  25. Huff MW, Hamilton RMG, Carroll KK (1977) Plasma cholesterol levels in rabbits fed low fat, cholesterol-free, semipurified diets: effects of dietary proteins, protein hydrolysates and amino acid mixtures. Atherosclerosis 28(2):187–195

    Article  CAS  PubMed  Google Scholar 

  26. Huff MW, Roberts DCK, Carroll KK (1982) Long-term effects of semipurified diets containing casein or soy protein isolate on atherosclerosis and plasma lipoproteins in rabbits. Atherosclerosis 41:327–336

    Article  CAS  PubMed  Google Scholar 

  27. Jones RJ, Huffman S (1956) Chronic effect of dietary protein on hypercholesterolaemia in the rat. Proc Soc Exp Biol Med 93:519–522

    Article  CAS  PubMed  Google Scholar 

  28. Katan MJ, Louis HM, Vroomen LH, Hermus RJJ (1982) Reduction of casein-induced hypercholesterolaemia and atherosclerosis in rabbits and rats by dietary glycine, arginine and alanine. Atherosclerosis 43:381–391

    Article  CAS  PubMed  Google Scholar 

  29. Key TJ, Fraser GE, Thorogood M et al (1999) Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Am J Clin Nutr 70:516S–524S

    CAS  PubMed  Google Scholar 

  30. Kurowska EM, Carroll KK (1992) Effect of high levels of selected dietary essential amino acids on hypercholesterolaemia and down-regulation of hepatic LDL receptors in rabbits. Biochim Biophys Acta 1126(2):185–191

    Article  CAS  PubMed  Google Scholar 

  31. Kurowska EM, Carroll KK (1994) Hypercholesterolemic responses in rabbits to selected groups of dietary essential amino acids. J Nutr 124:364–370

    CAS  PubMed  Google Scholar 

  32. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  CAS  PubMed  Google Scholar 

  33. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  CAS  PubMed  Google Scholar 

  34. Little JM, Angell EA (1977) Dietary protein level and experimental aortic atherosclerosis. Atherosclerosis 26(2):173–179

    Article  CAS  PubMed  Google Scholar 

  35. Lofland HB, Clarkson TB, Goodman HO (1961) Interactions among dietary fat, protein, and cholesterol in atherosclerosis-susceptible pigeons: effect on serum cholesterol and aortic atherosclerosis. Circ Res 9:919–924

    Article  CAS  PubMed  Google Scholar 

  36. Lorient D, Linden G (1976) Dephosphorylation of bovine casein by milk alkaline phosphatase. J Dairy Res 43:19–26

    Article  CAS  PubMed  Google Scholar 

  37. Mahley RW, Holcombe KS (1977) Alterations of the plasma lipoproteins and apoproteins following cholesterol feeding in the rat. J Lipid Res 18:314–324

    CAS  PubMed  Google Scholar 

  38. Meinhertz H, Nilausen K, Faergemen O (1990) Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol. J Nutr Sci Vitaminol 36(2):S157–S164

    Article  Google Scholar 

  39. Moreno JJ, Mitjavila MT (2003) The degree of unsaturation of dietary fatty acids and the development of atherosclerosis. J Nutr Biochem 14(4):182–195

    Article  CAS  PubMed  Google Scholar 

  40. Nath N, Harper AE, Elvehjem CA (1959) Diet and cholesteremia: part 3 effect of dietary proteins with particular reference to the lipids in wheat gluten. Can J Biochem Physiol 37:1375–1384

    Article  CAS  PubMed  Google Scholar 

  41. Oakenfull DG, Fenwick DE, Hood RL (1979) Effects of saponins on bile acids and plasma lipids in the rat. Br J Nutr 42:209–216

    Article  CAS  PubMed  Google Scholar 

  42. Oakenfull DG, Sidhu GS (1990) Could saponins be a useful treatment for hypercholesterolemia? Eur J Clin Nutr 44:79–88

    CAS  PubMed  Google Scholar 

  43. Sacks FM, Breslow JL, Wood PG, 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

    CAS  PubMed  Google Scholar 

  44. Samman S, Khosla KK, Carroll KK (1990) Intermediate density lipoprotein-apolipoprotein B turnover in rabbits fed semipurified diets containing casein or soy protein. Ann Nutr Metab 34(2):98–103

    Article  CAS  PubMed  Google Scholar 

  45. Sindayikengera S, Xia W (2006) Nutritional evaluation of caseins and whey proteins and their hydrolysates from Protamex. J Zhejiang Univ (Sci) 7(2):90–98

    Article  CAS  Google Scholar 

  46. Terpstra AHM, Harkes L, Van der Veen FH (1981) The effect of different proportions of casein in semipurified diets on the concentration of serum cholesterol and the lipoprotein composition in rabbits. Lipids 16:114–119

    Article  CAS  PubMed  Google Scholar 

  47. Terpstra AHM, Van Tintelin G, West CE (1981) The effect of semipurified diets containing different proportions of either casein or soybean protein on the concentrations of cholesterol in whole serum, serum lipoproteins and liver in male and female rats. Atherosclerosis 42:85–95

    Article  Google Scholar 

  48. Van Der Meer R, De Vries H, Van Tintelen G (1988) The phosphorylation state of casein and the species-dependency of its hypercholesterolaemic effect. Br J Nutr 59:467–473

    Article  PubMed  Google Scholar 

  49. Van Raaij JMA, Katan MB, Hautvast JGAJ, Hermus RJJ (1981) Effects of casein versus soy protein diets on serum cholesterol and lipoproteins in young healthy volunteers. Am J Clin Nutr 34:1261–1271

    PubMed  Google Scholar 

  50. Vega-Lopez S, Lichtenstein AH (2005) Dietary protein type and cardiovascular disease risk factors. Prev Cardiol 8(1):31–40

    Article  CAS  PubMed  Google Scholar 

  51. Xian CJ, Shoubridge CA, Read LC (1995) Degradation of IGF-1 in the adult rat gastrointestinal tract is limited by a specific antiserum or the dietary protein casein. J Endocrinol 146:215–225

    Article  CAS  PubMed  Google Scholar 

  52. Zhang X, Shu XO, Fao Y-T et al (2003) Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 133:2874–2878

    CAS  PubMed  Google Scholar 

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Correspondence to Andreas Bergdahl.

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Koury, O.H., Scheede-Bergdahl, C. & Bergdahl, A. The role of casein in the development of hypercholesterolemia. J Physiol Biochem 70, 1021–1028 (2014). https://doi.org/10.1007/s13105-014-0365-9

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