Life Extension Magazine November 2004
Novel Dietary Supplement Shows Dramatic Effects in Lowering Cholesterol, LDL, and Triglycerides
By Jim English
|LE Magazine November 2004|
|Novel Dietary Supplement Shows Dramatic Effects |
in Lowering Cholesterol, LDL, and Triglycerides
By Jim English
Safety and Effects of Sytrinol™
The cholesterol-lowering effects of Sytrinol™ were documented in a recent animal study published in the May 2004 issue of the Journal of Agricultural and Food Chemistry. Canadian researchers first induced high blood levels of cholesterol in hamsters. The animals were then treated with either polymethoxylated flavonoids (tangeretin) or a combination of flavones (hesperidin and naringin). While the flavones were shown to lower cholesterol levels, the tangeretin formulation proved to be almost three times as effective. In hamsters receiving the tangeretin formula, total cholesterol declined by up to 27% and LDL was reduced by 40%. While HDL levels were unchanged, the net result was a significant improvement in the LDL:HDL ratio.70
The cardioprotective and cholesterol-lowering claims for Sytrinol™ are also supported by human studies. Two early trials, each using 10 subjects, measured the effects of Sytrinol™ in men and women diagnosed with hyper-cholesterolemia and screened to eliminate thyroid disorders, kidney disorders, and diabetes. Subjects were instructed to maintain normal dietary habits and discontinue using vitamins, supplements, and cholesterol-lowering medications for at least six weeks before and during the study. Fasting blood samples were drawn at the onset and at the end of each four-week trial, and plasma lipid profiles and other metabolic parameters were analyzed using standard methods.
The results from the first trial (Table 1) show that four weeks of treatment with 300 mg of Sytrinol™ daily significantly reduced levels of total cholesterol (-25%), LDL (-19%), and triglycerides (-24%). HDL levels were unchanged and body mass remained relatively stable.
In the second trial, subjects with elevated cholesterol again benefited after only four weeks of treatment with 300 mg per day of Sytrinol™. As shown in Table 2, treatment with Sytrinol™ substantially cut levels of plasma total cholesterol (-20%), LDL (-22%), apolipoprotein B (-21%), and triglycerides (-28%). Additionally, subjects in the second trial benefited from a significant 5% increase in apolipoprotein A1, an important structural protein of HDL.
Sytrinol™ is currently being tested in a long-term, double-blind, crossover randomized study involving 120 men and women with moderately elevated cholesterol levels (total cholesterol above 230 mg/dL and LDL greater than 155 mg/dL). For 12 weeks, subjects will receive either 300 mg per day of Sytrinol™ or placebo, followed by a washout period of four weeks and another 12 weeks during which the groups receiving the active compound or placebo will be crossed over.
Only the first 12 weeks (phase 1) of the long-term study have been completed, yet already the results are compelling. As shown in Table 3, compared to placebo, the Sytrinol™ subjects saw reductions of 30% in total cholesterol, 27% in LDL, and 34% in total triglycerides. In addition, HDL levels increased 4%, resulting in a significant 29% reduction in the LDL:HDL ratio.
1. Available at: http://www.cdc.gov/nccdphp/aag/aag_cvd.htm). Accessed September 7, 2004.
2. Wald NJ, Law MR. Serum cholesterol and ischaemic heart disease. Atherosclerosis. 1995 Dec;118 Suppl:S1-5.
3. Barter P. Treatment of dyslipidaemia in high-risk patients: too little, too late. Int J Clin Pract Suppl. 2002 Jul;(130):15-9.
4. Ford ES, Mokdad AH, Giles WH, Mensah GA. Serum total cholesterol concentrations and awareness, treatment, and control of hypercholesterolemia among US adults: findings from the National Health and Nutrition Examination Survey, 1999 to 2000. Circulation. 2003 May 6;107(17):2185-9.
5. Nash IS, Mosca L, Blumenthal RS, Davidson MH, Smith SC Jr, Pasternak RC. Contemporary awareness and understanding of cholesterol as a risk factor: results of an American Heart Association national survey. Arch Intern Med. 2003 Jul 14;163(13):1597- 600.
6. Gotto AM Jr. Lipid management in patients at moderate risk for coronary heart disease: insights from the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Med. 1999 Aug 23;107(2A):36S-39S.
7. Steyer TE, King DE, Mainous AG 3rd, Gilbert G. Use of nutritional supplements for the prevention and treatment of hypercholesterolemia. Nutrition. 2003 May;19(5):415-8.
8. Kassirer JP. Why should we swallow what these studies say? Washington Post. August 1, 2004:B03. Available at: http://www.washingtonpost.com/wp-dyn/articles/A29456-2004Jul31.html. Accessed August 30, 2004.
9. Perreault S, Hamilton VH, Lavoie F, Grover S. Treating hyperlipidemia for the primary prevention of coronary disease. Are higher doses of lovastatin cost-effective? Arch Intern Med 1998 Feb 23;158(4):375-81.
10. Onder G, Landi F, Volpato S, et al. Serum cholesterol levels and in-hospital mortality in the elderly. Am J Med. 2003 Sep;115(4):265-71.
11. Brescianini S, Maggi S, Farchi G, Mariotti, et al. Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging. J Am Geriatr Soc. 2003 Jul;51(7):991-6.
12. Brown MD, Jin L, Jien ML, et al. Lipid retention in the arterial wall of two mouse strains with different atherosclerosis suscep- tibility. J Lipid Res. 2004 Jun;45(6):1155-61.
13. Weverling-Rijnsburger AW, Jonkers IJ, van Exel E, Gussekloo J, Westendorp RG. High- density vs low-density lipoprotein choles- terol as the risk factor for coronary artery disease and stroke in old age. Arch Intern Med. 2003 Jul 14;163(13):1549-54.
14. Pullinger CR, Kane JP, Malloy MJ. Primary hypercholesterolemia: genetic causes and treatment of five monogenic disorders. Expert Rev Cardiovasc Ther. 2003 May;1(1):107-19.
15. Gustafsson M, Flood C, Jirholt P, Boren J. Retention of atherogenic lipoproteins in atherogenesis. Cell Mol Life Sci. 2004 Jan;61(1):4-9.
16. Cabezas Castro M, Liem A. The use of apolipoprotein B in clinical practice to determine the risk for atherosclerosis. Ned Tijdschr Geneeskd. 2003 Jul 26;147(30):1445-8.
17. Walldius G, Jungner I. Apolipoproteins are new and better risk indicators of myocardial infarction. Lakartidningen. 2004 Mar 25;101(13):1188-94.
18. Walldius G, Jungner I. Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid- modifying therapy. J Intern Med. 2004 Feb;255(2):188-205.
19. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improve- ment in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001 Dec 15;358(9298):2026-33.
20. Williams K, Sniderman AD, Sattar N, D’Agostino R Jr, Wagenknecht LE, Haffner SM. Comparison of the associations of apolipoprotein B and low-density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2003 Nov 11;108(19):2312-6.
21. National Health and Nutrition Examination Study III (NHANES III, 1988–94) (CDC) NCHS.
22. Farmer JA. Aggressive lipid therapy in the statin era. Prog Cardiovasc Dis 1998 Sep;41(2):71-94.
23. Farnier M, Davignon J. Current and future treatment of hyperlipidemia: the role of statins. Am J Cardio .l 1998 Aug 27;82(4B):3J- 10J.
24. Grundy SM, Cleeman JI, Bairey Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39.
25. Herper M. Cholesterol guidelines a gift for Merck, Pfizer. Forbes. July 12, 2004.
26. Ricks D, Rabin R. Panel’s ties to drugmakers not cited in new cholesterol guidelines. Newsday. July 15, 2004.
27. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8931-4.
28. Bayer voluntarily withdraws Baycol. FDA Talk Papers T01-34. August 8, 2001.
29. Wolfe SM. Dangers of rosuvastatin identified before and after FDA approval. Lancet. 2004 Jun 26;363(9427):2189-90.
30. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA. 1996 Jan 3;275(1):55-60.
31. Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ. The risk of cancer in users of statins. Clin Oncol. 2004 Jun 15;22(12):2388-94.
32. Esserman L, Campbell M, Shoemaker M, Lobo M, Marx C, Benz C. Breast cancer inhibition by statins. J Clin Oncol. 2004 Jul 15;22(14 Suppl):1003.
33. Shannon J, Garzotto M, Palma AJ. Statin use and prostate cancer risk. J Clin Oncol. 2004 Jul 15;22(14 Suppl):4596.
34. Poynter J, Rennert G, Bonner J, et al. HMG CoA reductase inhibitors and the risk of colorectal cancer. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology. New Orleans, LA. June 2004.
35. Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR. The association between 3-hydroxy-3-methylglu- taryl coenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case-control study. Cancer. 2004 Jun 1;100(11):2308-16.
36. Katano H, Pesnicak L, Cohen JI. Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV lymphomas. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4960-5
37. Jiang Z, Zheng X, Lytle RA, Higashikubo R, Rich KM. Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells. Neurochem. 2004 Apr;89(1):168-78.
38. Gaist D, Jeppesen U, Andersen M, García Rodríguez LA, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: A case-control study. Neurology 2002 May 14;58(9):1333-7.
39. Ornish D. Lower cholesterol without drugs. Washington Post. August 8, 2004:B07.
40. Buening MK, Chang RL, Huang MT, Fortner JG, Wood AW, Conney AH. Activation and inhibition of benzo(a)pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoid. Cancer Res. 1981 Jan;41(1):67-72.
41. Siess MH, Guillermic M, Le Bon AM, Suschetet M. Induction of monooxygenase and transferase activities in rat by dietary administration of flavonoids. Xenobiotica. 1989 Dec;19(12):1379-86.
42. Guengerich FP, Kim DH. In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human liver microsomes by naringenin and other flavonoids. Carcinogenesis. 1990 Dec;11(12):2275-9.
43. Mukhtar H, Das M, Khan WA, Wang ZY, Bik DP, Bickers DR. Exceptional activity of tannic acid among naturally occurring plant phenols in protecting against 7,12-dimethyl- benz(a) anthracene-, benzo(a)pyrene-, 3- methylcholanthrene-, and N-methyl-N- nitrosourea-induced skin tumorigenesis in mice. Cancer Res. 1988 May 1;48(9):2361-5.
44. Verma AK, Johnson JA, Gould MN, Tanner MA. Inhibition of 7,12- dimethylbenz(a)anthracene and N-nitro somethylurea induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 1988 Oct 15;48(20):5754-8.
45. Firenzuoli F, Gori L, Crupi A, Neri D. Flavonoids: risks or therapeutic opportunities? Recenti Prog Med. 2004 Jul-Aug;95(7- 8):345-51.
46. Middleton E, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol. 1992 Mar 17;43(6):1167-79.
47. Maron DJ. Flavonoids for reduction of atherosclerotic risk. Curr Atheroscler Rep. 2004 Jan;6(1):73-8.
48. Milde J, Elstner EF, Grassmann J. Synergistic inhibition of low-density lipoprotein oxidation by rutin, gamma-terpinene, and ascorbic acid. Phytomedicine. 2004 Feb;11(2-3):105-13.
49. Monforte MT, Trovato A, Kirjavainen S, Forestieri AM, Galati EM, Lo Curto RB. Biological effects of hesperidin, a citrus flavonoid. (note II): hypolipidemic activity on experimental hypercholesterolemia in rat. Farmaco. 1995 Sep;50(9):595-9.
50. Tseng KF. Nobiletin. Part I., an oil extracted by cold methyl alcohol from Citrus nobilis, Lour, affords nobiletin, a hexam- ethoxyflavone containing a veratryl nucleus. Chem Soc. 1938;1003-4.
51. Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem. 2001 Feb;8(2):135-53.
52. Murakami A, Nakamura Y, Torikai K, et al. Inhibitory effect of citrus nobiletin on phor- bol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res. 2000 Sep 15;60(18):5059-66.
53. Minagawa A, Otani Y, Kubota T, et al. The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice. Jpn J Cancer Res. 2001 Dec;92(12):1322-8.
54. O'Leary KA, de Pascual-Tereasa S, Needs PW, Bao YP, O'Brien NM, Williamson G. Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutat Res. 2004 Jul 13;551(1-2):245-54.
55. Lin N, Sato T, Takayama Y, et al. Novel anti- inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem Pharmacol. 2003 Jun 15;65(12):2065-71.
56. Murakami A, Nakamura Y, Ohto Y, et al. Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti- inflammatory polymethoxyflavonoid. Biofactors. 2000;12(1-4):187-92.
57. Nelson EK. The occurrence of a pentamethyl flavonol in tangerine peel. J Am Chem Soc. 1934;56:1392.
58. Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Effect of citrus flavonoids on HL-60 cell differentiation. Anticancer Res. 1999 Mar-Apr;19(2A):1261-9.
59. Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Antiproliferative activity of flavonoids on several cancer cell lines. Biosci Biotechnol Biochem. 1999 May;63(5):896-9.
60. Manthey JA, Guthrie N. Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J Agric Food Chem. 2002 Oct 9;50(21):5837-43.
61. Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease. Neuroreport. 2001 Dec 4;12(17):3871-5.
62. Kurowska EM, Manthey JA, Casaschi A, Theriault AG. Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin. Lipids. 2004 Feb;39(2):143-51.
63. Gordon DA. Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly. Curr Opin Lipidol. 1997 Jun;8(3):131-7.
64. Jamil H, Gordon DA, Eustice DC, et al. An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11991-5.
65. Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Altern Med Rev. 2004 Mar;9(1):32-53.
66. Sun W, Yan Y, Dong F. Progression of tocotrienols. Wei Sheng Yan Jiu. 2004 Mar;33(2):243-5.
67. Ong AS, Goh SH. Palm oil: a healthful and cost-effective dietary component. Food Nutr Bull. 2002 Mar;23(1):11-22.
68. Iqbal J, Minhajuddin M, Beg ZH. Suppression of 7,12-dimethylbenz[alpha]anthracene-induced carcinogenesis and hypercholesterolaemia in rats by tocotrienol-rich fraction isolated from rice bran oil. Eur J Cancer Prev. 2003 Dec;12(6):447-53.
69. Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis. 2002 Mar;161(1):199-207.
70. Kurowska EM, Manthey JA. Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia. J Agric Food Chem. 2004 May 19;52(10):2879-86.