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A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia

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Abstract

Dyslipidemia is recognized as a major cause of cardiovascular disease. A number of evidence-based guidelines recommend conventional synthetic drugs as standard therapy for dyslipidemia in clinical practice. However, antihyperlipidemic drugs have some serious side effects. Naturally derived dietary supplements are becoming attractive as an alternative strategy because of their high efficacy and safety, as supported by numerous data. Moreover, they could be considered an initial treatment for dyslipidemia. The aims of this literature review were to demonstrate the efficacy, safety, and clinical implications of dietary supplements for treating dyslipidemia. We reviewed the literature, including data from in vitro, in vivo, and human studies, and clinical guideline recommendations. We classified dietary supplements by their proposed mechanisms of action on lipid metabolism and also collected daily dosage recommendations, interactions with concurrent drugs and/or foods, dosage forms, and examples of commercially available products. Various types of naturally derived dietary supplements exhibit lipid-improving properties. Efficacy and safety are acceptable; however, their use in clinical practice will require further well-designed investigations and the support of scientific data.

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References

  1. Executive summary of the third report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285(19):2486–97. doi:10.1001/jama.285.19.2486.

    Article  Google Scholar 

  2. Reiner Ž, Catapano AL, De Backer G, 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. 2011;32(14):1769–818.

    Article  PubMed  Google Scholar 

  3. Mahabir S, Pathak YV. Nutraceuticals and health: review of human evidence. In: Pathak YV, editor. Boca Raton: CRC Press; 2014. p. 373.

  4. Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: The available clinical data. Phytomedicine. 2016;23(11):1113–8.

    Article  CAS  PubMed  Google Scholar 

  5. DerMarderosian E, Beutler JA. The review of natural products. 8th ed. St. Louis: Wolters Kluwer Health; 2014. p. 2052.

    Google Scholar 

  6. Reynolds K, Chin A, Lees KA, et al. A meta-analysis of the effect of soy protein supplementation on serum lipids. Am J Cardiol. 2006;98(5):633–40.

    Article  CAS  PubMed  Google Scholar 

  7. Pipe EA, Gobert CP, Capes SE, et al. Soy protein reduces serum LDL cholesterol and the LDL cholesterol:HDL cholesterol and apolipoprotein B:apolipoprotein A-I ratios in adults with type 2 diabetes. J Nutr. 2009;139(9):1700–6.

    Article  CAS  PubMed  Google Scholar 

  8. de Mejia EG, Dia VP. Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappaB pathway in the macrophage. Peptides. 2009;30(12):2388–98.

    Article  PubMed  Google Scholar 

  9. Kitagawa T, Kosuge H, Uchida M, et al. RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease. Mol Imaging Biol. 2012;14(3):315–24.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Steinberg FM, Guthrie NL, Villablanca AC, et al. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr. 2003;78(1):123–30.

    CAS  PubMed  Google Scholar 

  11. Sacks FM, Lichtenstein A, Van Horn L. Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation. 2006;113(7):1034–44.

    Article  CAS  PubMed  Google Scholar 

  12. Cho SJ, Juillerat MA, Lee CH. Cholesterol lowering mechanism of soybean protein hydrolysate. J Agric Food Chem. 2007;55(26):10599–604.

    Article  CAS  PubMed  Google Scholar 

  13. Messina M. Soy foods, isoflavones, and the health of postmenopausal women. Am J Clin Nutr. 2014;100(Suppl 1):423S–30S.

    Article  CAS  PubMed  Google Scholar 

  14. AbuMweis SS, Barake R, Jones PJH. Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food Nutr Res. 2008;52:1–17.

    Article  Google Scholar 

  15. Ras RT, Geleijnse JM, Trautwein EA. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr. 2014;112(2):214–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Racette SB, Lin X, Lefevre M, et al. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am J Clin Nutr. 2010;91(1):32–8.

    Article  CAS  PubMed  Google Scholar 

  17. Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111(11):1720–9.

    Article  CAS  PubMed  Google Scholar 

  18. Kim W, Jeong MH, Cho SH, et al. Effect of green tea consumption on endothelial function and circulating endothelial progenitor cells in chronic smokers. Circ J. 2006;70(8):1052–7.

    Article  CAS  PubMed  Google Scholar 

  19. Alexopoulos N, Vlachopoulos C, Aznaouridis K, et al. The acute effect of green tea consumption on endothelial function in healthy individuals. Eur J Cardiovasc Prev Rehabil. 2008;15(3):300–5.

    Article  PubMed  Google Scholar 

  20. Koo SI, Noh SK. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect. J Nutr Biochem. 2007;18(3):179–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang TT, Koo MW. Chinese green tea lowers cholesterol level through an increase in fecal lipid excretion. Life Sci. 2000;66(5):411–23.

    Article  CAS  PubMed  Google Scholar 

  22. Bursill CA, Roach PD. A green tea catechin extract upregulates the hepatic low-density lipoprotein receptor in rats. Lipids. 2007;42(7):621–7.

    Article  CAS  PubMed  Google Scholar 

  23. Ripsin CM, Keenan JM, Jacobs DR Jr, et al. Oat products and lipid lowering. A meta-analysis. JAMA. 1992;267(24):3317–25.

    Article  CAS  PubMed  Google Scholar 

  24. Anderson JW, Allgood LD, Lawrence A, 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. 2000;71(2):472–9.

    CAS  PubMed  Google Scholar 

  25. Brown L, Rosner B, Willett WW, et al. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69(1):30–42.

    CAS  PubMed  Google Scholar 

  26. Momenizadeh A, Heidari R, Sadeghi M, et al. Effects of oat and wheat bread consumption on lipid profile, blood sugar, and endothelial function in hypercholesterolemic patients: a randomized controlled clinical trial. ARYA Atheroscler. 2014;10(5):259–65.

    PubMed  PubMed Central  Google Scholar 

  27. Shen H, He L, Price RL, et al. Dietary soluble fiber lowers plasma LDL cholesterol concentrations by altering lipoprotein metabolism in female guinea pigs. J Nutr. 1998;128(9):1434–41.

    CAS  PubMed  Google Scholar 

  28. Visavadiya NP, Narasimhacharya AVRL. Sesame as a hypocholesteraemic and antioxidant dietary component. Food Chem Toxicol. 2008;46(6):1889–95.

    Article  CAS  PubMed  Google Scholar 

  29. Khalesi S, Paukste E, Nikbakht E, et al. Sesame fractions and lipid profiles: a systematic review and meta-analysis of controlled trials. Br J Nutr. 2016;115(5):764–73.

    Article  CAS  PubMed  Google Scholar 

  30. Alipoor B, Haghighian MK, Sadat BE, et al. Effect of sesame seed on lipid profile and redox status in hyperlipidemic patients. Int J Food Sci Nutr. 2012;63(6):674–8.

    Article  CAS  PubMed  Google Scholar 

  31. Guo Z, Liu XM, Zhang QX, et al. Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis. 2011;21(11):844–50.

    Article  CAS  PubMed  Google Scholar 

  32. Cho YA, Kim J. Effect of probiotics on blood lipid concentrations: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015;94(43):e1714.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sun J, Buys N. Effects of probiotics consumption on lowering lipids and CVD risk factors: a systematic review and meta-analysis of randomized controlled trials. Ann Med. 2015;47(6):430–40.

    Article  PubMed  Google Scholar 

  34. Jones ML, Tomaro-Duchesneau C, Martoni CJ, et al. Cholesterol lowering with bile salt hydrolase-active probiotic bacteria, mechanism of action, clinical evidence, and future direction for heart health applications. Expert Opin Biol Ther. 2013;13(5):631–42.

    Article  CAS  PubMed  Google Scholar 

  35. Chiang MT, Yao HT, Chen HC. Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol. Biosci Biotechnol Biochem. 2000;64(5):965–71.

    Article  CAS  PubMed  Google Scholar 

  36. Gallaher CM, Munion J, Hesslink R Jr, et al. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr. 2000;130(11):2753–9.

    CAS  PubMed  Google Scholar 

  37. Bokura H, Kobayashi S. Chitosan decreases total cholesterol in women: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2003;57(5):721–5.

    Article  CAS  PubMed  Google Scholar 

  38. Tapola NS, Lyyra ML, Kolehmainen RM, et al. safety aspects and cholesterol-lowering efficacy of chitosan tablets. J Am Coll Nutr. 2008;27(1):22–30.

    Article  CAS  PubMed  Google Scholar 

  39. Hall C 3rd, Tulbek MC, Xu Y. Flaxseed. Adv Food Nutr Res. 2006;51:1–97. doi:10.1016/S1043-4526(06)51001-0.

    Article  CAS  PubMed  Google Scholar 

  40. Pan A, Yu D, Demark-Wahnefried W, et al. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr. 2009;90(2):288–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kawakami Y, Yamanaka-Okumura H, Naniwa-Kuroki Y, et al. Flaxseed oil intake reduces serum small dense low-density lipoprotein concentrations in Japanese men: a randomized, double blind, crossover study. Nutr J. 2015;14:39.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bloedon LT, Balikai S, Chittams J, et al. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr. 2008;27(1):65–74.

    Article  CAS  PubMed  Google Scholar 

  43. West SG, Krick AL, Klein LC, et al. Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function. J Am Coll Nutr. 2010;29(6):595–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fukumitsu S, Villareal MO, Onaga S, et al. alpha-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis pathway by suppressing SREBP-2, SREBP-1a and -1c expression. Cytotechnology. 2013;65(6):899–907.

    Article  CAS  PubMed  Google Scholar 

  45. Yeh YY, Liu L. Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies. J Nutr. 2001;131(3s):989S–93S.

    CAS  PubMed  Google Scholar 

  46. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013;71(5):282–99.

    Article  PubMed  Google Scholar 

  47. Reinhart KM, Talati R, White CM, et al. The impact of garlic on lipid parameters: a systematic review and meta-analysis. Nutr Res Rev. 2009;22(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  48. Zeng T, Guo FF, Zhang CL, et al. A meta-analysis of randomized, double-blind, placebo-controlled trials for the effects of garlic on serum lipid profiles. J Sci Food Agric. 2012;92(9):1892–902.

    Article  CAS  PubMed  Google Scholar 

  49. Williams MJ, Sutherland WH, McCormick MP, et al. Aged garlic extract improves endothelial function in men with coronary artery disease. Phytother Res. 2005;19(4):314–9.

    Article  CAS  PubMed  Google Scholar 

  50. Larijani VN, Ahmadi N, Zeb I, et al. Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: the FAITH randomized clinical trial. Nutrition. 2013;29(1):71–5.

    Article  CAS  PubMed  Google Scholar 

  51. Lau BH. Suppression of LDL oxidation by garlic compounds is a possible mechanism of cardiovascular health benefit. J Nutr. 2006;136(3 Suppl):765S–8S.

    CAS  PubMed  Google Scholar 

  52. WHO. World Health Organization (WHO) monographs on selected medicinal plants. Geneva: WHO; 1999.

  53. Gordon RY, Cooperman T, Obermeyer W, et al. Marked variability of monacolin levels in commercial red yeast rice products: Buyer beware! Arch Int Med. 2010;170(19):1722–7.

    Article  CAS  Google Scholar 

  54. Li Y, Jiang L, Jia Z, et al. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6):e98611.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Venero CV, Venero JV, Wortham DC, et al. Lipid-lowering efficacy of red yeast rice in a population intolerant to statins. Am J Cardiol. 2010;105(5):664–6.

    Article  CAS  PubMed  Google Scholar 

  56. Affuso F, Ruvolo A, Micillo F, et al. 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. 2010;20(9):656–61.

    Article  CAS  PubMed  Google Scholar 

  57. Liu J, Zhang J, Shi Y, et al. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. 2006;1:4.

  58. Ulbricht C, Basch E, Szapary P, et al. Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Complement Ther Med. 2005;13(4):279–90.

    Article  PubMed  Google Scholar 

  59. Wu J, Xia C, Meier J, et al. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol. 2002;16(7):1590–7.

    Article  CAS  PubMed  Google Scholar 

  60. Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem. 2003;278(12):10214–20.

    Article  CAS  PubMed  Google Scholar 

  61. Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med. 2009;17(1):16–22.

    Article  PubMed  Google Scholar 

  62. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003;290(6):765–72.

    Article  CAS  PubMed  Google Scholar 

  63. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747–57.

    Article  PubMed  Google Scholar 

  64. Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2009;136(1):4–16.

    Article  PubMed  Google Scholar 

  65. Rizza S, Tesauro M, Cardillo C, et al. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis. 2009;206(2):569–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rodriguez-Cruz M, Tovar AR, del Prado M, et al. Molecular mechanisms of action and health benefits of polyunsaturated fatty acids. Rev Invest Clin. 2005;57(3):457–72.

    CAS  PubMed  Google Scholar 

  67. Berge K, Musa-Veloso K, Harwood M, et al. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels. Nutr Res. 2014;34(2):126–33.

    Article  CAS  PubMed  Google Scholar 

  68. Cicero AF, Rosticci M, Morbini M, et al. Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial. Arch Med Sci. 2016;12(3):507–12.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Yoshida H, Yanai H, Ito K, et al. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Atherosclerosis. 2010;209(2):520–3.

    Article  CAS  PubMed  Google Scholar 

  70. Lobraico JM, DiLello LC, Butler AD, et al. Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial. BMJ Open Diabetes Res Care. 2015;3(1):e000107.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Ramprasath VR, Eyal I, Zchut S, et al. Supplementation of krill oil with high phospholipid content increases sum of EPA and DHA in erythrocytes compared with low phospholipid krill oil. Lipids Health Dis. 2015;14:142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ramprasath VR, Eyal I, Zchut S, et al. Enhanced increase of omega-3 index in healthy individuals with response to 4-week n-3 fatty acid supplementation from krill oil versus fish oil. Lipids Health Dis. 2013;12:178.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Vigerust NF, Bjorndal B, Bohov P, et al. Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-alpha. Eur J Nutr. 2013;52(4):1315–25.

    Article  CAS  PubMed  Google Scholar 

  74. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother. 1999;33(4):426–8.

    Article  CAS  PubMed  Google Scholar 

  75. Bartle WR, Madorin P, Ferland G. Seaweed, vitamin K, and warfarin. Am J Health Syst Pharm. 2001;58(23):2300.

    CAS  PubMed  Google Scholar 

  76. Huang SS, Sung SH, Chiang CE. Chitosan potentiation of warfarin effect. Ann Pharmacother. 2007;41(11):1912–4.

    Article  CAS  PubMed  Google Scholar 

  77. Lin X, Racette SB, Lefevre M, et al. combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation. 2011;124(5):596–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gonzalez Canga A, Fernandez Martinez N, Sahagun Prieto AM, et al. Dietary fiber and its interaction with drugs. Nutr Hosp. 2010;25(4):535–9.

  79. Cicero AF, Gaddi A. Rice bran oil and gamma-oryzanol in the treatment of hyperlipoproteinaemias and other conditions. Phytother Res. 2001;15(4):277–89.

    Article  CAS  PubMed  Google Scholar 

  80. Wang L, Wang X, Wu H, et al. Overview on biological activities and molecular characteristics of sulfated polysaccharides from marine green algae in recent years. Mar Drugs. 2014;12(9):4984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Abdul QA, Choi RJ, Jung HA, et al. Health benefit of fucosterol from marine algae: a review. J Sci Food Agric. 2016;96(6):1856–66.

    Article  CAS  PubMed  Google Scholar 

  82. Janikula M. Policosanol: a new treatment for cardiovascular disease. Altern Med Rev. 2002;7(3):203–17.

    PubMed  Google Scholar 

  83. Aramwit P, Petcharat K, Supasyndh O. Efficacy of mulberry leaf tablets in patients with mild dyslipidemia. Phytother Res. 2011;25(3):365–9.

    CAS  PubMed  Google Scholar 

  84. Spielmann J, Shukla A, Brandsch C, et al. Dietary lupin protein lowers triglyceride concentrations in liver and plasma in rats by reducing hepatic gene expression of sterol regulatory element-binding protein-1c. Ann Nutr Metab. 2007;51(4):387–92.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Pornanong Aramwit.

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This study was funded by the Thailand Research Fund through the Research and Researcher for Industry Programme (RRi) (Grant No. PHD57I0041) to Thanchanit Thaipitakwong and Pornanong Aramwit, Thailand.

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Thanchanit Thaipitakwong and Pornanong Aramwit have no conflicts of interest that might be relevant to the contents of this manuscript.

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Thaipitakwong, T., Aramwit, P. A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia. Am J Cardiovasc Drugs 17, 27–35 (2017). https://doi.org/10.1007/s40256-016-0191-2

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