Nutraceuticals for the treatment of hypercholesterolemia

European Journal of Internal Medicine

Volumn 25, Issue 7, 2014, Pages 592-599

  Mannarino, Massimo R ^a   Ministrini, Stefano ^a   Pirro, Matteo ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Berberine; Hypercholesterolemia; Nutraceuticals; Phytosterols; Red yeast rice

Indexed keywords

BERBERINE; CHOLESTEROL; CHOLESTIN; DAIDZIN; EZETIMIBE; GENISTEIN; GLYCITIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOFLAVONE DERIVATIVE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NUTRACEUTICAL; PHYTOSTEROL; POLICOSANOL; SIMVASTATIN; SOYBEAN PROTEIN; STANOZOLOL; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; HYPOCHOLESTEROLEMIC AGENT; SOY DERIVATIVE;

CHOLESTEROL BLOOD LEVEL; DIETARY FIBER; HIGH RISK PATIENT; HUMAN; HYPERCHOLESTEROLEMIA; LIPID BLOOD LEVEL; LIPID METABOLISM; LOW RISK PATIENT; NUTRIENT; PROGNOSIS; REVIEW; BLOOD; DIET SUPPLEMENTATION; ARTICLE; DRUG EFFICACY; DRUG SAFETY; DRUG USE; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; DIETARY SUPPLEMENTS; HUMANS; HYPERCHOLESTEROLEMIA;

EID: 84906933528     PISSN: 09536205     EISSN: 18790828     Source Type: Journal    
DOI: 10.1016/j.ejim.2014.06.008     Document Type: Review

References (102)

1. European cardiovascular disease statistics, 2008 edition [internet] S. Allender, P. Scarborough, V. Peto, M. Rayner, J. Leal, and R. Luengo-Fernandez et al. 2008 The European Heart Network [cited 2008 Jan 8, Available from: https://www.bhf.org.uk/publications/view-publication.aspx?ps=1001443 ]
2. C. Baigent, L. Blackwell, J. Emberson, L.E. Holland, C. Reith, and N. Bhala et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomized trials Lancet 376 9753 Nov 13 2010 1670 1681
3. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [internet] N.J. Stone, J. Robinson, A.H. Lichtenstein, C.N. Bairey Merz, D.M. Lloyd-Jones, and C.B. Blum et al. Circulation 2013 American Heart Association Dallas [2013, cited 2013 Nov 12. Available from: http://circ.ahajournals.org/ content/early/2013/11/11/01.cir.0000437738.63853.7a.citation ]
4. A.L. Catapano, G. De Backer, I. Graham, M.R. Taskinen, O. Wiklund, and E. Agewall et al. ESC/EAS guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J 32 2011 1769 1818 10.1093/eurheartj/ehr158
5. J.D. Neaton, H. Blackburn, D. Jacobs, L. Kuller, D.J. Lee, and R. Sherwin et al. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group Arch Intern Med 152 7 Jul 1992 1490 1500
6. M. Pirro, R. Del Giorno, G. Lupattelli, M.R. Mannarino, A.R. Roscini, and D. Covelli et al. Cardiovascular risk factors and recommended lipid goals attainment among patients referred in a tertiary care lipid clinic Eur J Int Med 22 4 Aug 2011 412 417
7. C.M. Shay, H. Ning, N.B. Allen, M.R. Carnethon, S.E. Chiuve, and K.J. Greenlund et al. Status of cardiovascular health in US adults: prevalence estimates from the National Health and Nutrition Surveys (NHANES) 2003-2008 Circulation 125 1 Jan 3 2012 45 56
8. M. Arca, and G. Pigna Treating statin-intolerant patients Diabetes Metab Syndr Obes 4 2011 155 166
9. T.T. Abd, and T.A. Jacobson Statin-induced myopathy: a review and update Expert Opin Drug Saf 10 2011 373 387
10. M.J. Blaha, K. Nasir, and R.S. Blumenthal Statin therapy for healthy men identified as "increased risk" JAMA 307 14 Apr 11 2012 1489 1490
11. R.F. Redberg, and M.H. Katz Healthy men should not take statins JAMA 307 14 Apr 11 2012 1491 1492
12. B.V. Howard, L. Van Horn, J. Hsia, J.E. Manson, M.L. Stefanick, and S. Wassertheil-Smoller et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial JAMA 295 2006 655 666
13. B. Chauhan, G. Kumal, N. Kalam, and S.H. Ansari Current concepts and prospects of herbal nutraceutical: a review J Adv Pharm Technol Res 4 1 Jan-Mar 2013 4 8
14. S.H. Zeisel Regulation of "nutraceuticals" Science 285 1999 1853 1855
15. U.S. Food and Drug administration [internet] Silver Spring: U.S. Food and Drug Administration; U.S. Department of Health and Human Services [updated 2014 March 3; cited 2014 March 6]. Available from: http://www.fda.gov/aboutfda/ transparency/basics/ucm193949.htm
16. Implementing rules for applications for authorization of health claims as provided for in Article 15 of Regulation No 1924/2006 of the European Parliament and the Council Commission Regulation No 353/2008 of 18 April 2008 2008
17. M. Houston The role of nutraceutical supplements in the treatment of dyslipidemia J Clin Hypertens 14 2012 121 132
18. M.C. Houston, S. Fazio, F.H. Chilton, D.E. Wise, K.B. Jones, and T.A. Barringer et al. Non pharmacologic treatment of dyslipidemia Prog Cardiovasc Dis 52 2009 61 94
19. R.J. Miksicek Estrogenic flavonoids: structural requirements for biological activity Proc Soc Exp Biol Med 208 1995 44 50
20. J.W. Anderson, B.M. Johnstone, and M.E. Cook-Newell Meta-analysis of the effects of soy protein on serum lipids N Engl J Med 333 1995 276 282
21. F.M. Sacks, A. Lichtenstein, L. Van Horn, W. Harris, P. Kris-Etherton, and M. Winston Soy protein, isoflavones, and cardiovascular health. A summary of a statement for professionals from the American Heart Association Nutrition Committee Arterioscler Thromb Vasc Biol 26 2006 1689 1692
22. R.M. Weggemans, and E.A. Trautwein Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis Eur J Clin Nutr 57 2003 940 946
23. D.J. Jenkins, C.W. Kendall, A. Marchie, D.A. Faulkner, J.M. Wong, and R. de Souza et al. Effects of a dietary portfolio of cholesterol lowering foods vs lovastatin on serum lipids and C-reactive protein J Am Med Assoc 290 2003 502 510
24. Y. Kokubo, H. Iso, J. Ishihara, K. Okada, M. Inoue, and S. Tsugane Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations. The Japan Public Health Center-Based (JPHC) Study Cohort I Circulation 116 2007 2553 2562
25. M.A. Eastwood, and R. Passmore Dietary fibre Lancet 2 1983 202 206
26. A. Keys, F. Grande, and J.T. Anderson Fibre and pectin in the diet and serum cholesterol concentration in man Proc Soc Exp Biol 106 1961 555 558
27. L. Brown, B. Rosner, W.W. Willett, and F.M. Sacks Cholesterol-lowering effects of dietary fiber: a meta-analysis Am J Clin Nutr 69 1999 30 42
28. S.R. Glore, D. Van Treeck, A.W. Knehans, and M. Guild Soluble fiber and serum lipids: a literature review J Am Diet Assoc 94 1994 425 436
29. P.M. Kris-Etherton, D. Krummel, M.E. Russell, D. Dreon, S. Mackey, and J. Borchers et al. The effect of diet on plasma lipids, lipoproteins, and coronary heart disease J Am Diet Assoc 88 1988 1373 1400
30. S. Liu, J.E. Buring, H.D. Sesso, E.B. Rimm, W.C. Willett, and J.E. Manson A prospective study of dietary fiber intake and risk of cardiovascular disease among women J Am Coll Cardiol 39 2002 49 56
31. D.R. Jacobs, M.A. Pereira, K.A. Meyer, and L.H. Kushi Fiber from whole grains, but not refined grains, is inversely associated with all-cause mortality in older women: the Iowa women's health study J Am Coll Nutr 19 2000 326S 330S
32. M.A. Pereira, E. O'Reilly, K. Augustsson, G.E. Fraser, U. Goldbourt, and B.L. Heitmann et al. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies Arch Intern Med 164 2004 370 376
33. R. Estruch, M.A. Martinez-Gonzalez, D. Corella, J. Basora-Gallisá, V. Ruiz-Gutiérrez, and M.I. Covas et al. Effects of dietary fibre intake on risk factors for cardiovascular disease in subjects at high risk J Epidemiol Community Health 63 2009 582 588
34. National Research Council Dietary reference intakes for energy, carbohydrate, fiber, Fat, fatty acids, cholesterol, protein, and amino acids (macronutrients) 2005 The National Academies Press Washington, DC
35. J.W. Anderson, L.D. Allgood, A. Lawrence, L.A. Altringer, G.R. Jerdack, and D.A. Hengehold et al. Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials Am J Clin Nutr 71 2 Feb 2000 472 479
36. T. Heinemann, G. Axtmann, and K. von Bergmann Comparison of intestinal absorption of cholesterol with different plant sterols in man Eur J Clin Invest 23 1993 827 831
37. K. von Bergmann, W. Prange, and D. Lütjohann Metabolism and mechanism of action of plant sterols Eur Heart J 1 Suppl. N 1999 S45 S49 [Suppl.]
38. C.S. Patch, L.C. Tapsell, P.G. Williams, and M. Gordon Plant sterols as dietary adjuvants in the reduction of cardiovascular risk: theory and evidence Vasc Health Risk Manag 2 2006 157 162
39. S.S. Ho, and S. Pal Margarine phytosterols decrease the secretion of atherogenic lipoproteins from HepG2 liver and Caco2 intestinal cells Atherosclerosis 182 1 Sep 2005 29 36
40. N.S. Sabeva, C.M. McPhaul, X. Li, T.J. Cory, D.J. Feola, and G.A. Graf Phytosterols differently influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells J Nutr Biochem 22 2011 777 783
41. M.B. Katan, S.M. Grundy, P. Jones, M. Law, T. Miettinen, and R. Paoletti et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels Mayo Clin Proc 78 2003 965 978
42. F.H. Mattson, R.A. Volpenhein, and B.A. Erickson Effect of plant sterol esters on the absorption of dietary cholesterol J Nutr 107 1977 139 1146
43. E. Mannarino, M. Pirro, C. Cortese, G. Lupattelli, D. Siepi, and A. Mezzetti et al. Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study Nutr Metab Cardiovasc Dis 19 2 Feb 2009 84 90
44. M.A. Hallikainen, and M.I. Uusitupa Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects Am J Clin Nutr 69 1999 403 410
45. M. Amir Shaghaghi, S.S. Abumweis, and P.J. Jones Cholesterol-lowering efficacy of plant sterols/stanols provided in capsule and tablet formats: results of a systematic review and meta-analysis J Acad Nutr Diet 113 11 Nov 2013 1494 1503 10.1016/j.jand.2013.07.006
46. O. Guardamagna, F. Abello, and V. Baracco et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption Acta Diabetol 48 2011 127 133
47. M. Becker, D. Staab, and K. Von Bergmann Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol J Pediatr 122 1993 292 296
48. H. Gylling, J. Plat, S. Turley, H.N. Ginsberg, L. Ellegård, and W. Jessup et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease Atherosclerosis 232 2 Feb 2014 346 360 10.1016/j.atherosclerosis.2013.11.043 [Epub 2013 Nov 23]
49. S.N. Blair, D.M. Capuzzi, S.O. Gottlieb, T. Nguyen, J.M. Morgan, and N.B. Cater Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy Am J Cardiol 86 2000 46 52
50. A.F. Vuorio, H. Gylling, H. Turtola, K. Kontula, P. Ketonen, and T.A. Miettinen Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation Arterioscler Thromb Vasc Biol 20 2000 500 506
51. H. Gylling, and T.A. Miettinen Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men J Lipid Res 37 1996 1776 1785
52. P. Wang, Y.M. Chen, L.P. He, C.G. Chen, B. Zhang, and W.Q. Xue et al. Association of natural intake of dietary plant sterols with carotid intima-media thickness and blood lipids in Chinese adults: a cross section study PLoS One 7 3 2012 e32736
53. O.T. Raitakari, P. Salo, H. Gylling, and T.A. Miettinen Plant stanol ester consumption and arterial elasticity and endothelial function Br J Nutr 100 2008 603 608
54. O.T. Raitakari, P. Salo, and M. Ahotupa Carotid artery compliance in users of plant stanol ester margarine Eur J Clin Nutr 62 2008 218 224
55. J. Plat, and R.P. Mensink Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects Atherosclerosis 148 2000 101 112
56. Expert Panel of the Diet and Cancer Project Food, nutrition and the prevention of cancer: a global perspective 1997 American Institute for Cancer Research Washington, DC 412 413
57. K.A. Varady, Y. Wang, and P.J. Jones Role of policosanols in the prevention and treatment of cardiovascular disease Nutr Rev 61 2003 376 383
58. M. Janikula Policosanol: a new treatment for cardiovascular disease? Altern Med Rev 7 2002 203 217
59. R. Menendez, A.M. Amor, I. Rodeiro, R.M. González, P.C. González, and J.L. Alfonso et al. Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts Arch Med Res 32 2001 8 12
60. H.K. Berthold, S. Unverdorben, R. Degenhardt, M. Bulitta, and I. Gouni-Berthold Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial JAMA 295 2006 2262 2269
61. L.X. Cubeddu, R.J. Cubeddu, T. Heimowitz, B. Restrepo, G.A. Lamas, and G.B. Weinberg Comparative lipid lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial Am Heart J 152 2006 982.e1 982.e5
62. M.F. Dulin, L.F. Hatcher, H. Sasser, and T.A. Barringer Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial Am J Clin Nutr 84 2006 1543 1548
63. J. Ma, Y. Li, Q. Ye, J. Li, Y. Hua, and D. Ju et al. Constituents of red yeast rice, a traditional Chinese Food and medicine J Agric Food Chem 48 2000 5220 5225
64. F.A. Went Monascus purpureus le champignon de l'angquac une nouvelle thelobolee Ann Soc Nat Bot 8 1895 1 17 [French]
65. A. Endo, and K. Monacolin A new hypocholesterolemic agent produced by a Monascus species J Antibiot (Tokyo) 32 1979 852 854
66. C.C. Lin, T.C. Li, and M.M. Lai Went rice in subjects with hyperlipidemia Eur J Endocrinol 153 2005 679 686
67. D. Heber, I. Yip, J.M. Ashley, D.A. Elashoff, R.M. Elashoff, and V.L. Go Cholesterol-lowering effects of a proprietary Chinese red-yeast rice dietary supplement Am J Clin Nutr 69 1999 231 236
68. J.J. Li, Z.L. Lu, W.R. Kou, Z. Chen, Y.F. Wu, and X.H. Yu et al. Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS) J Clin Pharmacol 49 8 2009 947 956
69. Clinton W. Yang, and Shaker A. Mousa The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other disorders Complement Ther Med 20 2012 466 474
70. D.J. Becker, R.Y. Gordon, S.C. Halbert, B. French, P.B. Morris, and D.J. Rader Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial Ann Intern Med 150 830-839 2009 W147 W839
71. K.E. Hansen, J.P. Hildebrand, E.E. Ferguson, and J.H. Stein Outcomes in 45 patients with statin-associated myopathy Arch Intern Med 165 2005 2671 2676
72. J. Liu, J. Zhang, Y. Shi, S. Grimsgaard, T. Alraek, and V. Fonnebo Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials Chin Med 1 Nov 23 2006 4
73. R.Y. Gordon, T. Cooperman, W. Obermeyer, and D.J. Becker Marked variability of monacolin levels in commercial red yeast rice products Arch Intern Med 170 2010 1722 1727
74. D. Heber, A. Lembertas, Q.Y. Lu, S. Bowerman, and V.L. Go An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents J Altern Complement Med 7 2 2001 133 139
75. J.W. Bennett, and M. Klich Mycotoxins Clin Microbiol Rev 16 3 2003 497 516
76. J. Yin, H. Zhang, and J. Ye Traditional Chinese medicine in treatment of metabolic syndrome Endocrinol Metab Immune Disord Drug Targets 8 2 2008 99 111
77. S. Lee, H.J. Lim, J.H. Park, K.S. Lee, Y. Jang, and H.Y. Park Berberine induced LDLR up-regulation involves JNK pathway Biochem Biophys Res Commun 362 2007 853 857
78. W. Kong, J. Wei, P. Abidi, M. Lin, S. Inaba, and C. Li et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins Nat Med 10 2004 1344 1351
79. J. Cameron, T. Ranheim, M.A. Kulseth, T.P. Leren, and K.E. Berge Berberine decrease PCSK9 expression in HepG2 cells Atherosclerosis 201 2008 266 273
80. J.M. Brusq, N. Ancellin, P. Grondin, R. Guillard, S. Martin, and Y. Saintillan et al. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine J Lipid Res 47 2006 1281 1288
81. H. Dong, Y. Zhao, L. Zhao, and L. Fuer The effects of berberine on blood lipids: a systematic review and meta-analysis of randomized controlled trials Planta Med 79 2013 437 446
82. W.J. Kong, J. Wei, Z.Y. Zuo, Y.M. Wang, D.Q. Song, and X.F. You et al. Combination of simvastatin with berberine improves the lipid-lowering effect Metabolism 57 2008 1029 1037
83. Y. Guo, Y. Chen, Z.R. Tan, C.D. Klaassen, and H.H. Zhou Repeated administration of berberine inhibits cytochromes P450 mRNA expression and activities in mice J Ethnopharmacol 138 2011 111 118
84. A.F. Cicero, L.C. Rovati, and I. Setnikar Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single blind clinical investigation Arzneimittelforschung 57 2007 26 30
85. F. Affuso, A. Ruvolo, F. Micillo, L. Saccà, and S. Fazio Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study Nutr Metab Cardiovasc Dis 20 2010 656 661
86. M. Pirro, G. Lupattelli, R. Del Giorno, G. Schillaci, S. Berisha, and M.R. Mannarino et al. Nutraceutical combination (red yeast rice, berberine and policosanols) improves aortic stiffness in low-moderate risk hypercholesterolemic patients Pharma Nutr 1 2013 73 77
87. G. Marazzi, L. Cacciotti, F. Pelliccia, L. Iaia, M. Volterrani, and G. Caminiti et al. Long-term effects of nutraceuticals (berberine, red yeast, policosanol) in elderly hypercholesterolemic patients Adv Ther 28 2011 1105 1113
88. L. Pisciotta, A. Bellocchio, and S. Bertolini Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment Lipids Health Dis 11 2012 123
89. O. Guardamagna, F. Abello, V. Baracco, B. Stasiowska, and F. Martino The treatment of hypercholesterolemic children: efficacy and safety of a combination of red yeast rice extract and policosanols Nutr Metab Cardiovasc Dis 21 2011 424 429
90. D.J. Becker, R.Y. Gordon, P.B. Morris, J. Yorko, J.Y. Gordon, and M. Li et al. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial Mayo Clin Proc 83 2008 758 764
91. D.J. Becker, B. French, P.B. Morris, E. Silvent, and R.Y. Gordon Phytosterols, red yeast rice, and lifestyle changes instead of statins: a randomized, double-blinded, placebo-controlled trial Am Heart J 166 2013 187 196
92. C. Agostoni, J.L. Bresson, S. Fairweather-Tait, A. Flynn, I. Golly, and H. Korhonen et al. Scientific opinion on the substantiation of a health claim related to isolated soy protein and reduction of blood LDL-cholesterol concentrations pursuant to Article 14 of Regulation (EC) No 1924/2006 EFSA J 10 2 2012 2555 10.2903/j.efsa.2012.2555
93. Health claims: soy protein and risk of coronary heart disease (CHD) 1999 [21 CFR sect, 101.82]
94. C. Agostoni, J.L. Bresson, S. Fairweather-Tait, A. Flynn, I. Golly, and H. Korhonen et al. Scientific opinion on the substantiation of health claims related to dietary fibre (ID 744, 745, 746, 748, 749, 753, 803, 810, 855, 1415, 1416, 4308, 4330) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 EFSA J 8 10 2010 1735 10.2903/j.efsa.2010.1735 [23 pp.]
95. Health claims: soluble fiber from certain foods and risk of coronary heart disease (CHD) 2008 [21 CFR sect. 101.81]
96. C. Agostoni, J.L. Bresson, S. Fairweather-Tait, A. Flynn, I. Golly, and H. Korhonen et al. Scientific opinion on the substantiation of a health claim related to 3 g/day plant sterols/stanols and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 19 of Regulation (EC) No 1924/2006 EFSA J 10 5 2012 2693 10.2903/j.efsa.2012.2693 [15 pp.]
97. Health claims: plant sterol/stanol esters and risk of coronary heart disease (CHD) 2005 [21 CFR sect. 101.83]
98. C. Agostoni, J.L. Bresson, S. Fairweather-Tait, A. Flynn, I. Golly, and H. Korhonen et al. Scientific opinion on the substantiation of health claims related to policosanols from sugar cane wax and maintenance of normal blood LDL-cholesterol concentrations (ID 1747, 1748, 1864, 1951, 1954, 4693) and maintenance of normal blood HDL-cholesterol concentrations (ID 1747, 1748, 1864, 1951, 1954, 4693) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 EFSA J 9 6 2011 2255 10.2903/j.efsa.2011.2255 [19 pp.]
99. U.S. Department of Health and Human Services. Food and Drugs Administration, editors. Fulfillment of Reporting Obligation under 21 U.S.C. 343(r) and 21 C.F.R. 101.93 to Pure Encapsulations, Inc. [internet]. New York District: 2002 [cited 2002 Oct 7]. Available at: 07/10/2002 http://www.fda.gov/ ohrms/dockets/dailys/03/Sept03/092603/97s-0162-let11074-vol84.pdf.
100. C. Agostoni, J.L. Bresson, S. Fairweather-Tait, A. Flynn, I. Golly, and H. Korhonen et al. Scientific opinion on the substantiation of health claims related to monacolin K from red yeast rice and maintenance of normal blood LDL cholesterol concentrations (ID 1648, 1700) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 EFSA J 9 7 2011 2304 10.2903/j.efsa.2011.2304 [16 pp.]
101. U.S. Department of Health and Human Services. Food and Drugs Administration, editors. FDA Warning Letter to Maypro Industries, Inc. [internet]. New York District: 2001 [cited 2001 Aug 5]. Available at: http://www.fda.gov/downloads/ICECI/EnforcementActions/WarningLetters/2001/ UCM069642.pdf.
102. U.S. Department of Health and Human Services. Food and Drugs Administration, editors. Fulfillment of Reporting Obligation under 21 U.S.C. 343(r) and 21 CFR 101.93 to Caren Advanced Nutraceuticals, a division of Econutrients, Inc. [internet]. New York District: 2000 [cited 2000 Oct 16]. Available at: http://www.fda.gov/ohrms/dockets/dailys/00/nov00/110900/let6116. pdf.