Life Extension Magazine November 2008
Preventing Cardiovascular Disease Naturally
By Julius Goepp, MD
Maximizing the Benefits of HDL
So let’s put this all together—for optimal cardiovascular health, we need to lower LDL and raise HDL levels, protect LDL from oxidation, raise activity of protective enzyme systems like PON1, and lower activity of risk-inducing systems such as CETP—not to mention reducing inflammatory stimuli and keeping endothelial cells’ health at a peak. That’s a tall order—but we can fill it readily by combining the strengths of supplements we already know about. Here’s how.
We’ve already seen that amla extracts, purified and processed to keep their vital polyphenol content intact, prevent oxidation, keep endothelial linings “slippery,” and optimize lipid profiles. By combining amla with extracts from a much less exotic plant family, we can further enhance antioxidant protection and add modulation of the powerful systems exemplified by PON1 and CETP. The so-called cruciferous vegetables (including cabbage, broccoli, Brussels sprouts, mustard greens, kale, and others) have long been associated with improved health and reduced vulnerability to cancers and cardiovascular diseases.52,53 These vegetables, and especially their properly grown and harvested sprouts, are rich in a number of polyphenols and sulfur-containing compounds with powerful antioxidant capabilities.54-56 Specific cruciferous vegetable-derived phytochemicals also have the surprising ability to stimulate activity of many of the phase 2 detoxification enzymes.57 In the words of cell biologist and cardiovascular researcher Lingyun Wu of the University of Saskatchewan, “a diet containing phase 2 protein inducers [such as those derived from cruciferous sprouts] also reduces the risk of developing cardiovascular problems of hypertension and atherosclerosis.”58
Nutritional scientists at FutureCeuticals in Illinois have recently issued a series of research reports in which they summarize their work with two proprietary sprout preparations known as “SproutGarden® 1” and “SproutGarden®-C.” Though these reports are preliminary and as yet unpublished, they are dramatic enough to merit inclusion in this discussion, and will certainly stimulate further large-scale research efforts. Here’s what they found:
Increased HDL Levels: SproutGarden® 1 (SPG1) was orally administered as a “shake” at 5 grams per dose twice daily to people with low HDL levels (below 40 mg/dL). Participants were advised to maintain typical diet, medicines, and habits during the study. HDL levels increased by an average of 29%, while other parameters such as LDL, fasting glucose, and liver function tests remained within normal ranges.59
Reduced LDL Oxidation: When SPG1 was added to serum from a young, healthy human, it reduced the chemically induced formation of oxidized LDL in the laboratory.60 When human subjects with elevated levels of oxidized LDL consumed SPG1 for three weeks, they experienced an average 69% decrease in levels of these dangerous complexes. Levels of other chemical markers of lipid oxidation associated with atherosclerosis also fell by 20-25%.61
Increased Protective PON1 Activity: When healthy, fasting human volunteers were tested before and after ingesting SPG1 as a single dose of 3 grams, activity of the cardioprotective enzyme PON1 in blood rose rapidly and dramatically (an average of 18% in the first 30 minutes).62
Reduction in Destructive CETP Activity: When SproutGarden®-C (SPG-C), a blend of sprouted seeds specifically selected for inhibition of LDL-enhancing CETP, was added in the laboratory to serum from healthy humans, a dramatic reduction in CETP activity of up to 50% was shown.63 A subsequent study in human volunteers showed that consumption of a single dose of 3 grams of SPG-C acutely inhibited activity of CETP in circulating blood.64 The researchers concluded that their results support the use of SPG-C as food material for modulating activity of CETP in humans, citing another recent study showing that even partial suppression of CETP activity positively affects the blood lipid profile.51
Maintaining a responsible diet and lifestyle are still the most effective means of optimizing cardiovascular health. Conventional medicine too often focuses on “after-the-fact” treatment interventions. Choosing an effective combination of nutritional supplements can be an important part of maintaining cardiovascular fitness through prevention. There is a solid scientific basis for including the combination of properly prepared amla extracts and carefully selected cruciferous sprout mixtures in an overall cardiovascular health regimen—their effects enhance and complement one another at the most fundamental molecular levels, and they boast a 3,000-year-long record of safe, effective, quality-of-life improvement.
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.
1. Coylewright M, Blumenthal RS, Post W. Placing COURAGE in context: review of the recent literature on managing stable coronary artery disease. Mayo Clin Proc. 2008 Jul;83(7):799-805.
2. Kapetanakis EI, Medlam DA, Boyce SW, et al. Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist’s panacea or the surgeon’s headache? Eur Heart J. 2005 Mar;26(6):576-83.
3. Shafiq N, Malhotra S, Pandhi P, Grover A. The “Statinth” wonder of the world: a panacea for all illnesses or a bubble about to burst. J Negat Results Biomed. 2005 Mar 23;4:3.
4. Czyz M, Watala C. Aspirin—the prodigious panacea? Molecular mechanisms of the action of acetylsalicylic acid in the organism. Postepy Hig Med Dosw (Online). 2005 Mar 23;59:105-15.
5. Lim MC. Drug-eluting stents: the panacea for restenosis? Singapore Med J. 2004 Jul;45(7):300-2.
6. Molavi B, Rasouli N, Mehta JL. Peroxisome proliferator-activated receptor ligands as antiatherogenic agents: panacea or another Pandora’s box? J Cardiovasc Pharmacol Ther. 2002 Jan;7(1):1-8.
7. Angiolillo DJ, Guzman LA, Bass TA. Current antiplatelet therapies: benefits and limitations. Am Heart J. 2008 Aug;156(2 Suppl):S3-S9.
8. Derosa G, Salvadeo S, Cicero AF. Recommendations for the treatment of hypertension in patients with DM: critical evaluation based on clinical trials. Curr Clin.Pharmacol. 2006 Jan;1(1):21-33.
9. El Desoky ES, Derendorf H, Klotz U. Variability in response to cardiovascular drugs. Curr Clin Pharmacol. 2006 Jan;1(1):35-46.
10. Scartezzini P, Speroni E. Review on some plants of Indian traditional medicine with antioxidant activity. J Ethnopharmacol. 2000 Jul;71(1-2):23-43.
11. Satiavati GV. The Legacy of Caraka (Book Review). Current Science. 2003;85:1087-90.
12. Muruganandam AV, Kumar V, Bhattacharya SK. Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats. Indian J Exp Biol. 2002 Oct;40(10):1151-60.
13. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine. Phytother Res. 1999 Jun;13(4):275-91.
14. Kumar KS, Muller K. Medicinal plants from Nepal; II. Evaluation as inhibitors of lipid peroxidation in biological membranes. J Ethnopharmacol. 1999 Feb;64(2):135-9.
15. Sabu MC, Kuttan R. Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol. 2002 Jul;81(2):155-60.
16. Augusti KT, Arathy SL, Asha R, et al. A comparative study on the beneficial effects of garlic (Allium sativum Linn), amla (Emblica Officinalis Gaertn) and onion (Allium cepa Linn) on the hyperlipidemia induced by butter fat and beef fat in rats. Indian J Exp Biol. 2001 Aug;39(8):760-6.
17. Anila L, Vijayalakshmi NR. Flavonoids from Emblica officinalis and Mangifera indica-effectiveness for dyslipidemia. J Ethnopharmacol. 2002 Jan;79(1):81-7.
18. Kim HJ, Yokozawa T, Kim HY, et al. Influence of amla (Emblica officinalis Gaertn.) on hypercholesterolemia and lipid peroxidation in cholesterol-fed rats. J Nutr Sci Vitaminol (Tokyo). 2005 Dec;51(6):413-8.
19. Saravanan S, Srikumar R, Manikandan S, Jeya PN, Sheela DR. Hypolipidemic effect of triphala in experimentally induced hypercholesteremic rats. Yakugaku Zasshi. 2007 Feb;127(2):385-8.
20. Rao TP, Sakaguchi N, Juneja LR, Wada E, Yokozawa T. Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats. J Med Food. 2005;8(3):362-8.
21. Gao X, Zhang H, Schmidt AM, Zhang C. AGE/RAGE produces endothelial dysfunction in coronary arterioles in Type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H491-8.
22. Su J, Lucchesi PA, Gonzalez-Villalobos RA, et al. Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1432-8.
23. Stirban A, Negrean M, Gotting C, et al. Dietary advanced glycation endproducts and oxidative stress: in vivo effects on endothelial function and adipokines. Ann NY Acad Sci. 2008 Apr;1126:276-9.
24. Smit AJ, Hartog JW, Voors AA, van Veldhuisen DJ. Advanced glycation endproducts in chronic heart failure. Ann NY Acad Sci. 2008 Apr;1126:225-30.
25. Ramasamy R, Yan SF, Herold K, Clynes R, Schmidt AM. Receptor for advanced glycation end products: fundamental roles in the inflammatory response: winding the way to the pathogenesis of endothelial dysfunction and atherosclerosis. Ann NY Acad Sci. 2008 Apr;1126:7-13.
26. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Effect of bioactive tannoid principles of Emblica officinalis on ischemia-reperfusion-induced oxidative stress in rat heart. Phytomedicine. 2002 Mar;9(2):171-4.
27. Antony B, Merina B, Sheeba V, Mukkadan J. Effect of standardized Amla extract on atherosclerosis and dyslipidemia. Indian J Pharm Sci. 2006;68(4):437-41.
28. Mathur R, Sharma A, Dixit VP, Varma M. Hypolipidaemic effect of fruit juice of Emblica officinalis in cholesterol-fed rabbits. J Ethnopharmacol. 1996 Feb;50(2):61-8.
29. Duan W, Yu Y, Zhang L. Antiatherogenic effects of phyllanthus emblica associated with corilagin and its analogue. Yakugaku Zasshi. 2005 Jul;125(7):587-91.
30. Yokozawa T, Kim HY, Kim HJ, Okubo T, Chu DC, Juneja LR. Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process. Br J Nutr. 2007 Jun;97(6):1187-95.
31. Cai X. Regulation of smooth muscle cells in development and vascular disease: current therapeutic strategies. Expert Rev Cardiovasc Ther. 2006 Nov;4(6):789-800.
32. Lembo G, Vecchione C, Morisco C, et al. Arterial hypertension and atherosclerosis: their epidemiology and physiopathology. Ann Ital Med Int. 1995 Oct;10 Suppl:69S-72S.
33. Jacob A, Pandey M, Kapoor S, Saroja R. Effect of the Indian gooseberry (amla) on serum cholesterol levels in men aged 35-55 years. Eur J Clin Nutr. 1988 Nov;42(11):939-44.
34. Manjunatha S, Jaryal AK, Bijlani RL, Sachdeva U, Gupta SK. Effect of Chyawanprash and vitamin C on glucose tolerance and lipoprotein profile. Indian J Physiol Pharmacol. 2001 Jan;45(1):71-9.
35. Nissen SE, Nicholls SJ, Wolski K, et al. Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA. 2007 Mar 28;297(12):1362-73.
36. R&D Laboratory, Arjuna Natural Extracts Ltd PBNO 126 Alwaya Cohin Karala India. Reduction of the risk of coronary heart disease (CHD) through a multi component targeting, including CRP-levels using Amlamax™ (AED-205) the standardized dry extract of Emblica officianalis Gaertn. (Indian gooseberry). 2007.
37. R&D Laboratory, Arjuna Natural Extracts Ltd PBNO 126 Alwaya Cohin Karala India. Amlama in management of dyslipidemia in humans. 2007
38. Dilaveris P, Giannopoulos G, Riga M, Synetos A, Stefanadis C. Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr Vasc Pharmacol. 2007 Jul;5(3):227-37.
39. Kazi D, Farmer JA. Raising high-density lipoprotein cholesterol: innovative strategies against an old adversary. Curr Atheroscler Rep. 2005 Mar;7(2):88-94.
40. Paragh G, Seres I, Harangi M, et al. Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome. Br J Clin Pharmacol. 2006 Jun;61(6):694-701.
41. Tomas M, Latorre G, Senti M, Marrugat J. The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis. Rev Esp Cardiol. 2004 Jun;57(6):557-69.
42. Mackness MI, Durrington PN, Mackness B. The role of paraoxonase 1 activity in cardiovascular disease: potential for therapeutic intervention. Am J Cardiovasc Drugs. 2004;4(4):211-7.
43. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005 Feb 15;69(4):541-50.
44. Dantoine T, Debord J, Merle L, Charmes JP. From organophosphate compound toxicity to atherosclerosis: role of paraoxonase 1. Rev Med Interne. 2003 Jul;24(7):436-42.
45. van Himbergen TM, van Tits LJ, Roest M, Stalenhoef AF. The story of PON1: how an organophosphate-hydrolysing enzyme is becoming a player in cardiovascular medicine. Neth J Med. 2006 Feb;64(2):34-8.
46. Mackness B, Hine D, Liu Y, Mastorikou M, Mackness M. Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells. Biochem Biophys Res Commun. 2004 Jun 4;318(3):680-3.
47. Aviram M, Kaplan M, Rosenblat M, Fuhrman B. Dietary antioxidants and paraoxonases against LDL oxidation and atherosclerosis development. Handb Exp Pharmacol. 2005;(170):263-300.
48. Graner M, James RW, Kahri J, et al. Association of paraoxonase-1 activity and concentration with angiographic severity and extent of coronary artery disease. J Am Coll Cardiol. 2006 Jun 20;47(12):2429-35.
49. Marchegiani F, Marra M, Spazzafumo L, et al. Paraoxonase activity and genotype predispose to successful aging. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):541-6.
50. Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol. 2006 Feb 7;47(3):492-9.
51. Morton RE, Greene DJ. Partial suppression of CETP activity beneficially modifies the lipid transfer profile of plasma. Atherosclerosis. 2007 May;192(1):100-7.
52. Hayes JD, Kelleher MO, Eggleston IM. The cancer chemopreventive actions of phytochemicals derived from glucosinolates. Eur J Nutr. 2008 May;47 Suppl 2:73-88.
53. Mukherjee S, Gangopadhyay H, Das DK. Broccoli: a unique vegetable that protects mammalian hearts through the redox cycling of the thioredoxin superfamily. J Agric Food Chem. 2008 Jan 23;56(2):609-17.
54. Zhu H, Jia Z, Strobl JS, et al. Potent Induction of Total Cellular and Mitochondrial Antioxidants and Phase 2 Enzymes by Cruciferous Sulforaphane in Rat Aortic Smooth Muscle Cells: Cytoprotection Against Oxidative and Electrophilic Stress. Cardiovasc Toxicol. 2008 Jul 8.
55. Baek SH, Park M, Suh JH, Choi HS. Protective effects of an extract of young radish (Raphanus sativus L) cultivated with sulfur (sulfur-radish extract) and of sulforaphane on carbon tetrachloride-induced hepatotoxicity. Biosci Biotechnol Biochem. 2008 May;72(5):1176-82.
56. Tiku AB, Abraham SK, Kale RK. Protective effect of the cruciferous vegetable mustard leaf (Brassica campestris) against in vivo chromosomal damage and oxidative stress induced by gamma-radiation and genotoxic chemicals. Environ Mol Mutagen. 2008 Jun;49(5):335-42.
57. Dinkova-Kostova AT, Fahey JW, et al. Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):847-51.
58. Wu L, Noyan Ashraf MH, Facci M, et al. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Natl Acad Sci USA. 2004 May 4;101(18):7094-9.
59. R&D Department, VDF FutureCeuticals. Blend of sprouted cruciferous seeds, SproutGarden, increases HDL blood levels. 2008.
60. R&D Department, VDF FutureCeuticals. Long-lasting inhibitory effect of blend of sprouted cruciferous seeds on Cu-induced LDL Oxidation ex vivo. 2008.
61. R&D Department, VDF FutureCeuticals. Blend of Sprouted Cruciferous Seeds, SproutGarden, reduces blood levels of oxLDL. 2008.
62. R&D Department, VDF FutureCeuticals. SproutGarden (#1) stimulates activity of Paraoxonase 1 in human blood. Acute effect case.
63. R&D Department, VDF FutureCeuticals. SproutGarden-C inhibits activity of Cholesteryl Ester Transfer Protein (CETP) in vivo. Clinical acute case study. 2008.
64. R&D Department, VDF FutureCeuticals. SproutGarden-C inhibits activity of Cholesteryl Ester Transfer Protein (CETP) in vivo. Clinical acute case study. 2008.
65. Sigal LH. Basic science for the clinician 44: atherosclerosis: an immunologically mediated (autoimmune?) disease. J Clin Rheumatol. 2007 Jun;13(3):160-8.
66. Liang CP, Han S, Senokuchi T, Tall AR. The macrophage at the crossroads of insulin resistance and atherosclerosis. Circ Res. 2007 Jun 8;100(11):1546-55.
67. Ferri C, Croce G, Cofini V, et al. C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis. Curr Pharm Des. 2007;13(16):1631-45.
68. Martins e Silva, Saldanha C. Diet, atherosclerosis and atherothrombotic events. Rev Port Cardiol. 2007 Mar;26(3):277-94.
69. Coppola G, Novo S. Statins and peripheral arterial disease: effects on claudication, disease progression, and prevention of cardiovascular events. Arch Med Res. 2007 Jul;38(5):479-88.
70. Jain RK, Finn AV, Kolodgie FD, Gold HK, Virmani R. Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature: a potential strategy for plaque stabilization. Nat Clin Pract Cardiovasc Med. 2007 Sep;4(9):491-502.
71. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA. 2007 Aug 15;298(7):786-98.
72. Windler E, Schoffauer M, Zyriax BC. The significance of low HDL-cholesterol levels in an ageing society at increased risk for cardiovascular disease. Diab Vasc Dis Res. 2007 Jun;4(2):136-42.
73. Jacobson TA, Miller M, Schaefer EJ. Hypertriglyceridemia and cardiovascular risk reduction. Clin Ther. 2007 May;29(5):763-77.
74. Rivera JJ, Blumenthal RS, Ashen D. Low-density lipoprotein cholesterol in high-risk asymptomatic individuals. J Cardiometab Syndr. 2007;2(1):49-52.
75. Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005 Oct 4;46(7):1225-8.
76. Ali R, Alexander KP. Statins for the primary prevention of cardiovascular events in older adults: a review of the evidence. Am J Geriatr Pharmacother. 2007 Mar;5(1):52-63.
77. Kunte H, Amberger N, Ruckert RI, Harms L. Statins and their influence on inflammatory processes in internal carotid artery stenosis. Zentralbl Chir. 2007 Jun;132(3):193-7.
78. Barter PJ, Rye KA. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):39-46.
79. Doncheva NI, Nikolov KV, Vassileva DP. Lipid-modifying and pleiotropic effects of gemfibrozil, simvastatin and pravastatin in patients with dyslipidemia. Folia Med (Plovdiv). 2006;48(3-4):56-61.
80. Vaverkova H. Dual inhibition of cholesterol using the drug combination ezetimibe/simvastatin? Vnitr Lek. 2007 Apr;53(4):421-7.
81. Bhatt DL. Anti-inflammatory agents and antioxidants as a possible “third great wave” in cardiovascular secondary prevention. Am J Cardiol. 2008 May 22;101(10A):4D-13D.
82. Fedoruk LM, Wang H, Conaway MR, Kron IL, Johnston KC. Statin therapy improves outcomes after valvular heart surgery. Ann Thorac Surg. 2008 May;85(5):1521-5; discussion 1525-6.
83. Graf K, Dietrich T, Tachezy M, et al. Monitoring therapeutical intervention with ezetimibe using targeted near-infrared fluorescence imaging in experimental atherosclerosis. Mol Imaging. 2008 Mar-Apr;7(2):68-76.
84. Scheen AJ, Radermecker RP. Drug of the month. Ezetimibe/simvastatin tablet (Inegy). Rev Med Liege. 2007 Sep;62(9):585-90.
85. Stroup J, Stephens J. Combination drug products: an indication for medication reconciliation and pharmacist counseling. J Am Pharm Assoc (2003). 2008 Jul-Aug;48(4):541-3.
86. Available at: http://www.fda.gov/cder/drug/early_comm/ezetimibe_simvastatin_SEAS.htm. Accessed September 9, 2008.
87. Available at: http://www.fda.gov/Cder/drug/InfoSheets/HCP/simvastatin_amiodaroneHCP.htm. Accessed September 9, 2008.