Life Extension Magazine March 2010
Lower Cholesterol Safely
By Robert Haas, MS
Beta-Sitosterol: An Anti-Inflammatory and Anti-Cholesterol Plant Extract
Beta-sitosterol is a primary plant sterol. This class of compounds is molecularly similar to cholesterol and may inhibit cholesterol’s absorption in the lower intestine and reduce levels of cholesterol in the blood. Phytosterols have also been shown to act in synergy with red yeast rice by achieving a therapeutic effect at a lower dose.
In effect, beta-sitosterol acts as a potent dietary cholesterol blocker. A significant body of clinical evidence has demonstrated its cholesterol-lowering effects. In a 2005 study, researchers gave 29 individuals with high cholesterol (40-80 years old, average age = 55; 14 with type 2 diabetes) an edible beta-sitosterol spread.20 Both diabetic and non-diabetic patients experienced a greater reduction in LDL—27% and 15% respectively—than controls.
A meta-analysis of 14 randomized controlled trials investigated the effects of plant sterols added to margarine on cholesterol levels.21 The sterol-fortified margarine caused a reduction in the mean concentration of LDL, an effect that tended to increase with age.
The results of two older beta-sitosterol studies further indicate it can decrease systemic inflammation. In one meta-analysis, the lead investigator noted that beta-sitosterol appears to support proliferation of peripheral blood lymphocytes and enhance the cytotoxic effect of natural killer cells.22 Another study that measured inflammation and immune suppression in marathon runners found that beta-sitosterol could help prevent immune system suppression and could reduce bodily inflammation.23 Together, these anti-inflammatory properties led researchers to suggest that beta-sitosterol might be of clinical use in treating a number of chronic inflammatory conditions that could lead to cancers of the breast and colon.
Policosanol is a naturally occurring component of beeswax and whole sugar cane. More than 80 studies performed mostly by a single research institute suggest that policosanol obtained from Cuban sugar cane at doses of 5-40 mg/dL exerts cholesterol-lowering effects equivalent to that of statin drugs.24,25 (It should be noted that other research groups using policosanol from alternative sources have failed to reproduce the efficacy of these alcohols observed in earlier studies.)26
Numerous animal models studies have been conducted using policosanol. One study found that pretreatment with policosanol and omega-3 fatty acids prevented arterial wall thickening and endothelial damage in animals whose arteries had been damaged artificially.27
Some research suggests that policosanol is effective in lowering cholesterol in patients with progressive atherosclerosis and diabetes. One study tested policosanol in patients suffering ischemic stroke who were also treated with aspirin and vitamins. They achieved substantially positive results, with improvements in neurological outcomes and recurrent events.28
Niacin’s ability to lower LDL, raise HDL, and lower triglyceride levels has been conclusively established by a wealth of clinical research.29 It is one of the best-known and most widely used vitamins for lowering blood cholesterol levels. It has also been shown in multiple studies to provide better heart health protection than some statins. A widely publicized study appearing last November in the New England Journal of Medicine found that niacin was more effective at shrinking artery plaque than a billion-dollar blockbuster called ezetimibe, the active ingredient in the cholesterol drugs Zetia® and Vytorin®.30
Recent studies further indicate that niacin reduces oxidative stress and inhibits vascular inflammatory genes, including key cytokines involved in atherosclerosis.29,31,32 Until recently, niacin’s general use and widespread patient tolerability have been impeded by the need to take it 4 times a day and by the high incidence of skin flushing, gastric problems, and other adverse events.
A form of “no-flush” niacin has emerged, called inositol hexaniacinate (IHN).33 It consists of six molecules of nicotinic acid (niacin) and one molecule of inositol. It is metabolized in the body into its component parts, niacin and inositol, and does not reach maximum blood levels for approximately 10 hours after ingestion. This form of the vitamin has not been linked with the skin “flushing” or other typical niacin reactions, even when ingested in amounts typically associated with skin flushing, nausea, vomiting, and agitation. Regrettably, it also does not work as well as niacin in reducing LDL and triglycerides and boosting HDL.
Statin drugs are heavily used and over-prescribed, owing to industry influence and misinformation. High-dose statins are often unnecessary, and may not be the right choice for millions of people, given their side effect profile. Studies indicate that any reduced cardiovascular risk from taking statins may be offset by other serious side effects, from sexual, visual, hepatic, renal, and cognitive dysfunction to disability and death. Aging individuals who want to lower their blood lipid levels and C-reactive protein (CRP) number may be able to achieve similar benefits with standardized red yeast rice extract, beta-sitosterol, pantethine, policosanol, and niacin. These synergistic ingredients have been shown to reduce blood lipid levels while promoting healthy endothelial function and reducing CRP and systemic inflammation. They offer a safer alternative to taking synthetic prescription statins.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Becker DJ, Gordon RY, Morris PB, et al. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial. Mayo Clin Proc. 2008 Jul;83(7):758-64.
2. Li JJ, Lu ZL, Kou WR, 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. 2009;49:947-56.
3. Lu Z, Kou W, Du B, et al. Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol. 2008;101:1689-93.
4. Zhao SP, Lu ZL, Du BM, et al. Xuezhikang, an extract of cholestin, reduces cardiovascular events in type 2 diabetes patients with coronary heart disease: subgroup analysis of patients with type 2 diabetes from China coronary secondary prevention study (CCSPS). J Cardiovasc Pharmacol. 2007;49:81-4.
5. Keithley JK, Swanson B, Sha BE, Zeller JM, Kessler HA, Smith KY. A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia. Nutrition. 2002;18:201-4.
6. Journoud M, Jones PJH. Red yeast rice: A new hypolipidemic drug. Life Sciences. 2004;74:2675-83.
7. Heber D, Yip I, Ashley JM, Elashoff DA, Go VLW. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69:231-6.
8. Wang J, Lu Z, Chi J, et al. Multicenter clinical trial of serum lipid-lowering effects of a Monascus purpureus (red yeast) rice preparation from traditional Chinese medicine. Curr Ther Res. 1997;58(12):964-78.
9. Available at: http://www.courant.com/news/politics/ny-hs-statin3,0,5977685.story. Accessed November 30, 2009.
10. Available at: http://www.yorku.ca/yfile/archive/index.asp?Article=12368. Accessed November 30, 2009.
11. Brewer HB. Benefit-risk assessment of Rosuvastatin 10 to 40 milligrams. Am J Cardiol. 2003;92:23-9K.
12. Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, et al. Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem. 2000;48:5220-5.
13. Man RY, Lynn Eg, Cheung F, Tsang PS. Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2). Mol Cell Biochem. 2002 Apr;233(1-2):153-8.
14. 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.
15. Becker DJ, Gordon RY, et al. Red yeast rice for dyslipidemia in statin-intolerant patients. Annals Int Med. 2009 Jun;150(16):830-9.
16. Zhao SP, Liu L, Cheng YC, Li YL. Effect of xuezhikang, a cholestin extract, on reflecting postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease. Atherosclerosis. 2003;168:375-80.
17. Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti M. Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age. Minerva Med. 1990;81:475-9.
18. Bertolini S, Donati C, Elicio N, et al. Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children. Int J Clin Pharmacol Ther Toxicol. 1986;24:630-7.
19. Gensini GF, Prisco D, Rogasi PG, Matucci M, Neri Serneri GG. Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment. Int J Clin Pharmacol Res. 1985;5:309-18.
20. Lau VW, Journoud M, Jones PJ. Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Am J Clin Nutr. 2005 Jun;81(6):1351-8.
21. Law MR. Plant sterol and stanol margarines and health. West J Med. 2000 Jul;173(1):43-7.
22. Bouic PJ. The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):471-5.
23. Bouic PJ, Clark A, Lamprecht J, et al. The effects of β-sitosterol (BSS) and—sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation. Int J Sports Med. 1999;20:258-62.
24. Castaño G, Fernández L, Mas R, et al. Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia. Drugs R D. 2005;6(4):207-19.
25. Castaño G, Fernández L, Mas R, Illnait J, Mesa M, Fernández JC. Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus. Clin Drug Investig. 2003;23(10):639-50.
26. Kassis AN, Marinangeli CP, Jain D, Ebine N, Jones PJ. Lack of effect of sugar cane policosanol on plasma cholesterol in Golden Syrian hamsters. Atherosclerosis. 2007;194:153-8.
27. Gamez R, Maz, R, Arruzazabala ML, Mendoza S, Castano G. Effects of concurrent therapy with policosanol and omega-3 fatty acids on lipid profile and platelet aggregation in rabbits. Drugs R D. 2005;6(1):11-9.
28. Ortega LL, Sánchez J, Más R, et al. Effects of policosanol on patients with ischemic stroke: a pilot open study. J Med Food. 2006 Fall;9 (3):378-85.
29. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101:20-6B.
30. Kastelein JJP, Bots ML. Statin ezetimibe or niacin in high-risk patients. NEJM. 2009 Nov 26;361(22):2180-3.
31. Kamanna VS, Vo A, Kashyap ML. Nicotinic acid: recent developments. Curr Opin Cardiol. 2008;23:393-8.
32. Kamanna VS, Ganji SH, Kashyap ML. Niacin: an old drug rejuvenated. Curr Atheroscler Rep. 2009;11:45-51.
33. No authors listed. Inositol hexaniacinate. Altern Med Rev. 1998 Jun;3(3):222-3.
34. Blanco M, Nombela F, Castellanos M, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology. 2007;69:904-910.
35. Heeschen C, Hamm CW, Laufs U, et al. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002;105:1446-52.
36. Brown WV. Safety of statins. Curr Opin Lipidol. 2008;19:558-62.
37. Ahn SC. Neuromuscular complications of statins. Phys Med Rehabil Clin N Am. 2008;19:47-59, vi.
38. Oldemeyer JB, Lund RJ, Koch M, Meares AJ, Dunlay R. Rhabdomyolysis and acute renal failure after changing statin-fibrate combinations. Cardiology. 2000;94:127-8.
39. Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother. 2002;36:288-95.
40. Schech S, Graham D, Staffa J, et al. Risk factors for statin-associated rhabdomyolysis. Pharmacoepidemiol Drug Saf. 2007;16:352-8.
41. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med. 2002;346:539-40.
42. Hanai J, Cao P, Tanksale P, et al. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 2007 Dec;117(12):3940-51.
43. King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy. 2003;23:1663-7.
44. Fraunfelder FW, Richards AB. Diplopia, blepharoptosis, and ophthalmoplegia and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor use. Ophthalmology. 2008;115:2282-5.
45. Gaist D, García Rodríguez LA, Huerta C, Hallas J, Sindrup SH. Are users of lipid-lowering drugs at increased risk of peripheral neuropathy? Eur J Clin Pharmacol. 2001;56:931-3.
46. de Langen JJ, van Puijenbroek EP. HMG-CoA-reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre. Neth J Med. 2006;64:334-8.
47. Chong PH, Boskovich A, Stevkovic N, Bartt RE. Statin-associated peripheral neuropathy: review of the literature. Pharmacotherapy. 2004;24:1194-203.
48. Chazerain P, Hayem G, Hamza S, Best C, Ziza JM. Four cases of tendinopathy in patients on statin therapy. Joint Bone Spine. 2001;68:430-3.
49. Golomb BA, McGraw JJ, Evans MA, Dimsdale JE. Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance. Drug Saf. 2007;30:669-75.
50. Smith DJ, Olive KE. Chinese red rice-induced myopathy. South Med J. 2003;96:1265-7.
51. Yang HT, Lin SH, Huang SY, Chou HJ. Acute administration of red yeast rice (Monascus purpureus) depletes tissue coenzyme Q(10) levels in ICR mice. Br J Nutr. 2005;93:131-5.
52. Prasad GV, Wong T, Meliton G, et al. Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient. Transplantation. 2002;74:1200-1.
53. Yang HT, Lin SH, Huang SY, et al. Acute administration of red yeast rice (Monascus purpureus) depletes tissue coenzyme Q(10) levels in ICR mice. Br J Nutr. 2005;93:131-5.
54. Available at: www.nutraingredients-usa.com/content/search?SearchText=CoQ10. Accessed December 29, 2009.
55. Available at: www.nutraingredients-usa.com/content/search?SearchText=statins. Accessed December 29, 2009.
56. Available at: www.nutraingredients-usa.com/content/search?SearchText=diabetes. Accessed December 29, 2009.