The Future for Heart-Healthy Nutraceuticals
The research for nutraceutical heart health benefits is beginning to pile up. The lack of side effects observed from the research, on top of thousands of years of traditional use assures consumers that nutraceuticals provide a margin of safety. Intelligent blends of heart-healthy nutraceuticals are beginning to take hold on the market, and nutraceutical companies are rapidly investing in research to further substantiate their benefits.
A perfect example of this is Flavoxine, a proprietary combination of an extract from the Amur cork tree (Phellodendron amurense) and a patented extract from Citrus sinensis (orange peel). Orange peel contains heart-healthy polymethoxylated flavones, or PMFs, while the Amur cork tree is known in Traditional Chinese Medicine for its anti-inflammatory properties. Deanne Dolnick, MS, of Salinas, CA-based Next Pharmaceuticals, commented on her company’s investment in clinical research. “We conducted a study on Flavoxine in which we observed statistically significant results for many cardiovascular parameters, including the lowering of LDL and triglycerides, the increase of HDL, and the lowering of C-reactive protein, which is a prime indicator of inflammation,” Ms. Dolnick said.
Next Pharmaceuticals plans to officially launch Flavoxine in the practitioner channel when this study is published—expected by the end of the second quarter this year. According to the company’s release of the double-blind, placebo-controlled trial, the obese Flavoxine-treated group experienced a 49% reduction of LDL, 12% increase in HDL, 18% reduction of triglycerides and 48% reduction in C-reactive protein levels. Blood pressure reduction was also significant. The normal weight treatment group experienced lower but significant results in these areas as well.
With this type of research and innovation being explored by nutraceutical companies, the future for heart healthy nutraceuticals appears bright indeed.
1. Onder G, et al. Serum cholesterol levels and in-hospital mortality in the elderly. Am J Med. 2003 Sept;115:265-71
2. Miller K. Cholesterol and in-hospital mortality in elderly patients. Am Family Phys. 2004 May.
3. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996 Sep 18;276(11):875-81.
4. Kullo IJ, Ballantyne CM. Conditional risk factors for atherosclerosis. Mayo Clin Proc. 2005 Feb;80(2):219-30.
5. Jensen HK. The molecular genetic basis and diagnosis of familial hypercholesterolemia in Denmark. Dan Med Bull. 2002 Nov;49(4):318-45.
6. Vauthier JM, Lluch A, Lecomte E, Artur Y, Herbeth B. Family resemblance in energy and macronutrient intakes: The Stanislas Family Study. Int J Epidemiol.1996 Oct;25(5):1030-7.
7. Keogh JB, Grieger JA, Noakes M, Clifton PM. Flow-mediated dilatation is impaired by a high-saturated fat diet but not by a high-carbohydrate diet. Arterioscler Thromb Vasc Biol. 2005 Mar:17.
8. Nestel PJ. Adulthood-prevention: Cardiovascular disease. Med J Aust. 2002 Jun 3;176(11 Suppl):S118-9.
9. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA. 2002 Nov 27;288(20):2569-78.
10. Noone EJ, Roche HM, Nugent AP, Gibney MJ. The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. Br J Nutr. 2002 Sep;88(3):243-51.
11. Muller H, Lindman AS, Blomfeldt A, Seljeflot I, Pedersen JI. A diet rich in coconut oil reduces diurnal postprandial variations in circulating tissue plasminogen activator antigen and fasting lipoprotein (a) compared with a diet rich in unsaturated fat in women. J Nutr. 2003 Nov;133(11):3422-7.
12. Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005 Mar;135(3):562-6.
13. Stachowska E, Dolegowska B, Chlubek D, Wesolowska T, Ciechanowski K, Gutowski P, Szumilowicz H, Turowski R. Dietary trans fatty acids and composition of human atheromatous plaques. Eur J Nutr. 2004 Oct;43(5):313-8.
14. Naruszewicz M, Daniewski M, Nowicka G, Kozlowska-Wojciechowska M. Trans-unsaturated fatty acids and acrylamide in food as potential atherosclerosis progression factors. Based on own studies. Acta Microbiol Pol. 2003;52 Suppl:75-81.
15. Innis SM, Hansen JW. Plasma 15. Innis SM, Hansen JW. Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy adults. Am J Clin Nutr. 1996 Aug;64(2):159-67.
acid responses, metabolic e
16. Vidgren HM, Agren JJ, Schwab U, Rissanen T, Hanninen O, Uusitupa MI. Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men. Lipids. 1997 Jul;32(7):697-705.
17. Schwellenbach LJ, Olson KL. McConnell KJ, Stolepart RS, Nash JD, Merenich JA. The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides. J Am Coll Nutr. 2006;25(6):480-485.
18. Chapidze G, Kapanadze S, Dolidze N, Bachutashvili Z, Latsabidze N. Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme q10 and statins. Georgian Med News. 2005 Jan;(1):20-5.
19. Alleva R, Tomasetti M, Bompadre S, Littarru GP. Oxidation of LDL and their subfractions: kinetic aspects and CoQ10 content. Mol Aspects Med. 1997;18 Suppl:S105-12.
20. Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fønnebø V. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. 2006 Nov 23;1:4.
21. Itokawa Y. Magnesium intake and cardiovascular disease. Clin Calcium. 2005 Feb;15(2):154-9.
22. Landmark K, Reikvam A. Do vitamins C and E protect against the development of carotid stenosis and cardiovascular disease? Tidsskr Nor Laegeforen. 2005 Jan 20;125(2):159-62.
23. Norris R. “Flush-free niacin”: Dietary supplement may be “benefit-free.” Prev Cardio. 2006 Winter:64.
24. Kerckhoffs DA, Brouns F, Hornstra G, Mensink RP. Effects on the human serum lipoprotein profile of beta-glucan, soy protein and isoflavones, plant sterols and stanols, garlic and tocotrienols. J Nutr. 2002 Sep;132(9):2494-505.
25. Vuksan V, Whitham D, Sievenpiper JL, Jenkins AL, Rogovik AL, Bazinet RP, Vidgen E, Hanna A. Supplementation of conventional therapy with the novel grain Salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes: Results of a randomized controlled trial. Diabetes Care. 2007 Nov;30(11):2804-10.
26. Chu YF, Liu RH. Cranberries inhibit LDL oxidation and induce LDL receptor expression in hepatocytes. Life Sci. 2005;77(15):1892-1901.
27. Seo K, Jung S, Park M, Song Y, Choung S. Effects of leucocyanidines on activities of metabolizing enzymes and antioxidant enzymes. Biol Pharm Bull. 2001 May;24(5):592-3.
28. Robert AM, Robert L, Renard G. Protection of cornea against proteolytic damage. Experimental study of procyanidolic oligomers (PCO) on bovine cornea. J Fr Ophthalmol. 2002 Apr;25(4):351-5.
29. Robert AM, Tixier JM, Robert L, Legeais JM, Renard G. Effect of procyanidolic oligomers on the permeability of the blood-brain barrier. Pathol Biol. 2001 May;49(4):298-304.
30. Drubaix I, Robert L, Maraval M, Robert AM. Synthesis of glycoconjugates by human diseased veins: modulation by procyanidolic oligomers. Int J Exp Pathol. 1997 Apr;78(2):117-21.
31. Drubaix I, Maraval M, Robert L, Robert AM. Hyaluronic acid (hyaluronan) levels in pathological human saphenous veins. Effects of procyanidol oligomers, Pathol Biol. 1997 Jan;45(1):86-91.
32. Robert AM, Groult N, Six C, Robert L. The effect of procyanidolic oligomers on mesenchymal cells in culture II-Attachment of elastic fibers to the cells. Pathol Biol. 1990 Jun;38(6):601-7.
33. Corbe C, Boissin JP, Siou A. Light vision and chorioretinal circulation. Study of the effect of procyanidolic oligomers (Endotelon). J Fr Ophtalmol. 1988;11(5):453-60.
34. Wegrowski J, Robert AM, Moczar M. The effect of procyanidolic oligomers on the composition of normal and hypercholesterolemic rabbit aortas. Biochem Pharmacol. 1984 Nov 1;33(21):3491-7.
35. Cahn J, Borzeix MG. Administration of procyanidolic oligomers in rats. Observed effects on changes in the permeability of the blood-brain barrier. Sem Hop. 1983 Jul 7;59(27-28):2031-4.
36. Melcion C, Verroust P, Baud L, Ardaillou N, Morel-Maroger L, Ardaillou R. Protective effect of procyanidolic oligomers on the heterologous phase of glomerulonephritis induced by anti-glomerular basement membrane antibodies. C R Seances Acad Sci III. 1982 Dec 6;295(12):721-6.
37. Royer RJ, Schmidt CL. Evaluation of venotropic drugs by venous gas plethysmography. A study of procyanidolic oligomers Sem Hop. 1981 Dec 18-25;57(47-48):2009-13.
38. Vinson JA, Proch J, Bose P. MegaNatural Gold grapeseed extract: In vitro antioxidant and in vivo human supplementation studies. J Med Food. 2001 Spring;4(1):17-26.
39. Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003 Mar;19(3):261-4.
40. Cesarone MR, Belcaro G, Nicolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandolini R, Vinciguerra G, Dugall M, Griffin M, Ruffini I, Acerbi G, Corsi M, Riordan NH, Stuard S, Bavera P, Di Renzo A, Kenyon J, Errichi BM. Prevention of venous thrombosis in long-haul flights with Flite Tabs: The LONFLIT-FLITE randomized, controlled trial. Angiology. 2003 Sep-Oct;54(5):531-9.
41. Maurer HR. Bromelain: Biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001 Aug;58(9):1234-45.
42. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988 Feb-Mar;22(2):191-203.
43. Felton GE. Fibrinolytic and anti-thrombotic action of bromelain may eliminate thrombosis in heart patients. Med Hypotheses. 1980 Nov;6(11):1123-33.
44. Nadkarni K, ed., Indian Materia Medica. reprinted 1989, Popular Prakashan Private, Ltd, Bombay.
45. Bharani A, Ganguli A, Mathur LK, Jamra Y, Raman PG. Efficacy of Terminalia arjuna in chronic stable angina: A double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate. Indian Heart J. 2002 Mar-Apr; 54(2):170-5.
46. Gupta R, Singhal S, Goyle A, Sharma VN. Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark powder: A randomised placebo-controlled trial. J Assoc Physicians India. 2001 Feb;49:231-5.
47. Kumar PU, Adhikari P, Pereira P, Bhat P. Safety and efficacy of Hartone in stable angina pectoris: an open comparative trial. J Assoc Physicians India. 1999 Jul;47(7):685-9.
48. Bharani A, Ganguly A, Bhargava KD. Salutary effect of Terminalia arjuna in patients with severe refractory heart failure. Int J Cardiol. 1995 May;49(3):191-9.
49. Dwivedi S, Jauhari R. Beneficial effects of Terminalia arjuna in coronary artery disease. Indian Heart J. 1997 Sep-Oct;49(5):507-10.
50. Dwivedi S, Agarwal MP. Antianginal and cardioprotective effects of Terminalia arjuna, an indigenous drug, in coronary artery disease. J Assoc Physicians India. 1994 Apr;42(4):287-9.
51. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India. 1989 May;37(5):323-8.
52. Wu J, Xia C, Meier J, Li S, Hu X, Lala D. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Molecular Endocrinology. 16(7):1590-1597.
53. Chander R, Khanna AK, Kapoor NK. Lipid lowering activity of guggulsterone from Commiphora mukul in hyperlipidaemic rats. Phytotherapy Res. 1996 10:508-511.
54. Lloyd J. American Materia Medica, Therapeutics and Pharmacognosy. Eclectic Medical Publications, Portland OR 1983.
55. Shahat AA, Hammouda F, Ismail SI, Azzam SA, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vlietinck AJ. Anti-complementary activity of Crataegus sinaica. Planta Med. 1996 Feb;62(1):10-3.
56. Miller AL. Botanical influences on cardiovascular disease. Altern Med Rev. 1998 Dec;3(6):422-31.
57. Belz GG, Loew D. Dose-response related efficacy in orthostatic hypotension of a fixed combination of D-camphor and an extract from fresh crataegus berries and the contribution of the single components. Phytomedicine. 2003;10 Suppl 4:61-7.
58. Belz GG, Butzer R, Gaus W, Loew D. Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension. Phytomedicine. 2002 Oct;9(7):581-8.
59. Walker AF, Marakis G, Morris AP, Robinson PA. Promising hypotensive effect of hawthorn extract: A randomized, double-blind pilot study of mild, essential hypertension. Phytother Res. 2002 Feb;16(1):48-54.
60. Rietbrock N, Hamel M, Hempel B, Mitrovic V, Schmidt T, Wolf GK. Actions of standardized extracts of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure. Arzneimittelforschung. 2001 Oct;51(10):793-8.
61. Schwinger RH, Pietsch M, Frank K, Brixius K. Crataegus special extract WS 1442 increases force of contraction in human myocardium cAMP-independently. J Cardiovasc Pharmacol. 2000 May;35(5):700-7.
62. Weikl A, Assmus KD, Neukum-Schmidt A, Schmitz J, Zapfe G, Noh HS, Siegrist J. Crataegus special extract WS 1442. Assessment of objective effectiveness in patients with heart failure (NYHA II). Fortschr Med. 1996 Aug 30;114(24):291-6.
63. Tauchert M. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J. 2002 May;143(5):910-5.
64. Nishioka K, Hidaka T, Nakamura S, Umemura T, Jitsuiki D, Soga J, Goto C, Chayama K, Yoshizumi M, Higashi Y. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007 Sep;30(9):775-80.
65. Bergner P. The Healing Power of Garlic. Rocklin, CA: Prima Publishing, 1996.
66. Ackermann RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L, Lawrence VA. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med. 2001 Mar 26;161(6):813-24.
67. Anim-Nyame N, Sooranna SR, Johnson MR, Gamble J, Steer PJ. Garlic supplementation increases peripheral blood flow: a role for interleukin-6? J Nutr Biochem. 2004 Jan;15(1):30-6.
68. Chang HS, Yamato O, Sakai Y, Yamasaki M, Maede Y. Acceleration of superoxide generation in polymorphonuclear leukocytes and inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion and garlic in dogs and humans. Prostaglandins Leukot Essent Fatty Acids. 2004 Jan;70(1):77-83.
69. Benatuil L, Apitz-Castro R, Romano E. Ajoene inhibits the activation of human endothelial cells induced by porcine cells: Implications for xenotransplantation. Xenotransplantation. 2003 Jul;10(4):368-73.
70. Rahman K. Garlic and aging: New insights into an old remedy. Ageing Res Rev. 2003 Jan;2(1):39-56.
71. Ou CC, Tsao SM, Lin MC, Yin MC. Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic. Lipids. 2003 Mar;38(3):219-24.
72. Kwon MJ, Song YS, Choi MS, Park SJ, Jeong KS, Song YO. Cholesteryl ester transfer protein activity and atherogenic parameters in rabbits supplemented with cholesterol and garlic powder. Life Sci. 2003 May 16;72(26):2953-64.
73. Ho SE, Ide N, Lau BH. S-allyl cysteine reduces oxidant load in cells involved in the atherogenic process. Phytomedicine. 2001 Jan;8(1):39-46.
74. Ide N, Lau BH. Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation. J Nutr. 2001 Mar;131(3s):1020S-6S.
75. Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels acting as a cardiotonic pump activator in mice, rabbit and dogs. J Cardiovasc Pharmacol. 2005 Jan;45(1):74-80.
76. Kobayashi M, Shoji N, Ohizumi Y. Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. Biochim Biophys Acta. 1987 Sep 18;903(1):96-102.
77. Koo KL, Ammit AJ, Tran VH, Duke CC, Roufogalis BD. Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation. Thromb Res. 2001 Sep 1;103(5):387-97.
78. Fuhrman B, Rosenblat M, Hayek T, Coleman R, Aviram M. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr. 2000 May;130(5):1124-31.
79. Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol. 1998 Jun;61(2):167-71.
80. Fuhrman B, Rosenblat M, Hayek T, Coleman R, Aviram M. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr. 2000 May;130(5):1124-31.
81. Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol. 1998 Jun;61(2):167-71.
82. Pancho LR, Kimura I, Unno R, Kurono M, Kimura M. Reversed effects between crude and processed ginger extracts on PGF2 alpha-induced contraction in mouse mesenteric veins. Jpn J Pharmacol. 1989 Jun;50(2):243-6.
83. Suekawa M, Sone H, Sakakibara I, Ikeya Y, Aburada M, Hosoya E. Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogaol and capsaicin. Nippon Yakurigaku Zasshi. 1986 Nov;88(5):339-47.
84. Suekawa M, Ishige A, Yuasa K, Sudo K, Aburada M, Hosoya E. Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol. J Pharmacobiodyn. 1984 Nov;7(11):836-48.
85. Rao CV. Regulation of COX and LOX by curcumin. Adv Exp Med Biol. 2007;595:213-26.
86. Yoshioka M, Doucet E, Drapeau V, Dionne I, Tremblay A. Combined effects of red pepper and caffeine consumption on 24-hour energy balance in subjects given free access to foods. Br J Nutr. 2001 Feb;85(2):203-11.
87. Govindarajan VS, Sathyanarayana MN. Capsicum: production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences. Crit Rev Food Sci Nutr. 1991;29(6):435-74.
88. Lal AA, Kumar T, Murthy PB, Pillai KS. Hypolipidemic effect of Coriandrum sativum L. in triton-induced hyperlipidemic rats. Indian J Exp Biol. 2004 Sep;42(9):909-12.