Botanical And Dietary Supplement Alternatives To Statins

I’ve had numerous requests for information regarding specific dietary supplements and herbs that can help to normalize cholesterol profiles. Because there is so much misinformation regarding cholesterol, I want to reiterate that cholesterol is not the evil monster that it is made out to be.

Cholesterol is a lipid that is critical for the proper functioning of the body, and is used to build cell membranes, create sex hormones, aid in immune health and tissue repair; and facilitate digestion. However, elevated LDL cholesterol and low HDL cholesterol, in the presence of prolonged inflammation, oxidation (of LDL cholesterol) and elevated blood glucose and insulin levels can contribute mightily to cardiovascular disease.

 

As I discussed at length in part 1 and 2 of this series, lipid levels can almost always be normalized with a combination of diet, weight loss, exercise, and appropriate supplementation. There is rarely the need for statins. As lipid levels fall, so does the risk of developing CHD, as well as the risk of suffering a stroke. Even if CHD is present, it’s not too late; lipid-lowering treatment in people with CHD can be lifesaving. Finally, botanical and nutritional agents used to regulate serum lipids are free of the negative side effects associated with statins and have the additional benefit of improving other cardiovascular risk factors.

The following nutrients and botanicals are those that I specifically recommend for improving cholesterol profiles in combination with my previous foundational dietary and lifestyle recommendations:

 

Red Yeast (Monascus purpureus)

Red yeast rice, a fermented rice product, has been used in Chinese cuisine for centuries as a medicinal food to promote “blood circulation.” Research shows that red yeast and red yeast rice contain substances called monacolins that are similar to prescription medications that lower cholesterol. However, while red yeast rice contains monacolin K (the active ingredient in the prescription cholesterol drug lovastatin), red yeast does not contain monacolin K.

Red yeast contains at least nine monacolins as well as many other important substances that contribute to its lipid lowering effects, including sterols (beta-sitosterol, campesterol, stigmasterol, sapogenin), isoflavones, and mono-unsaturated fats. Numerous studies show that red yeast favorably compares to statin drugs in lowering cholesterol, but without the adverse effects associated with the drugs. ^1-12 

Recent large clinical trials in China show that a partially purified extract of red yeast rice (Xuezhikang or XZK) lowers total and low-density lipoprotein cholesterol and triglycerides while increasing high-density lipoprotein cholesterol levels in patients with coronary heart disease. In one study of 5,000 patients, cardiovascular events and total mortality were reduced by 30% and 33%, while the need for by-pass surgeries was decreased by one-third. The researchers noted that long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths, improved lipoprotein regulation, and was safe and well tolerated. ^13-15

In a study reported in 2008 in Mayo Clinic Proceedings, researchers compared the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a statin. At the end of the 12-week trial, researchers noted that lifestyle changes combined with ingestion of red yeast rice and fish oil reduced LDL-C in proportions similar to standard therapy with simvastatin. ¹⁶

 

Artichoke leaf (Cynara scolymus) extract

Artichoke leaf has long been used in traditional medicine for jaundice and liver insufficiency as well as for cholesterol reduction. Scientific research supports these traditional uses, showing that artichoke appears to inhibit oxidation of low-density lipoprotein and reduces cholesterol biosynthesis. Researchers have identified several bioactives in artichoke extract, including chlorogenic acid, cynarin, caffeic acid, a sesquiterpene lactone, cynaropicrin, polyphenol oxidase, caffeoylquinic acids and luteolin. The absorption of these bioactive compounds results in beneficial metabolites such as ferulic acid.

Ferulic acid, chlorogenic acid and cynarin provide strong antioxidant protection, which may account for some of their health-promoting activities. In cultured liver cells, artichoke leaf extract (ALE) not only provided antioxidant defense from chemical toxins, but also protected cellular glutathione reserves. In addition to inhibiting cholesterol biosynthesis and LDL oxidation, ALE appears to positively modulate endothelial function and improve liver health. One proposed mechanism of action for ALE includes the effect of beta-glucosidase-dependent liberation of luteolin to inhibit hepatic cholesterol biosynthesis.

In several clinical trials ALE has been found to significantly reduce levels of ‘bad’ cholesterol in people with high cholesterol. In a study at the University of Reading, researchers noted that artichoke leaf extract could lower moderately raised cholesterol in otherwise healthy individuals. During the trial, 75 volunteers were given 1280mg of ALE, or matched placebo, each day for 12 weeks. ALE consumption resulted in a modest but statistically significant reduction in total plasma cholesterol after the intervention period. According to the researchers, ALE provides another option (over and above a healthy diet) to help lower cholesterol. ^17-26

While decreasing LDL and total cholesterol is often the aim of cholesterol management, it’s equally important to increase levels of beneficial HDL cholesterol. In a 2012 study, ALE was shown to do just that. In a randomized, double-blind, placebo-controlled clinical trial of 92 overweight subjects, researchers found that supplementation with 250 mg of ALE twice daily for 8 weeks decreased total and LDL-cholesterol while simultaneously increasing HDL levels. ²⁷

 

Guggul (Commiphora mukul)

Derived from the sap of the mukul myrrh tree, guggul has been used for centuries in Ayurvedic medicine. Traditionally prescribed for treating atherosclerosis, guggul has been shown to normalize lipid levels, including lowering VLDL and LDL cholesterol while at the same time increasing beneficial HDL cholesterol.

Guggul contains compounds called guggulsterones, including Z-guggulsterone and E-guggulsterone, which have been identified as the active constituents. Researchers believe that guggul works by 1) improving the liver’s ability to process, metabolize and excrete cholesterol, in particular LDL cholesterol; and 2) improving thyroid function by increasing T-4 to T-3 conversion.

I find that guggul is most effective used in combination with niacin, plant sterols, red yeast and other lipid lowering agents. Guggul has also been shown to decrease platelet adhesiveness and to increase fibrinolytic activity. Interestingly, guggul has demonstrated not only an ability to prevent atherosclerosis, but also to encourage the regression of pre-existing atherosclerotic plaque in animal studies. ^28-33

In six randomized clinical trials of guggul, results suggest reductions in total serum cholesterol from 10% to 27% compared with baseline level. One study also showed an increase in HDL cholesterol, and another found that guggul and its cholesterol-lowering component, guggulsterone, effectively inhibited LDL oxidation. ^34-39

 

Tocotrienols

Tocotrienols, a naturally occurring analogue of vitamin E, are a group of minor dietary constituents found in high fiber cereals and grains (barley, oats, rice, and wheat) and oils extracted from palm fruit and rice bran. While most people are familiar with vitamin E in the form of d-alpha tocopherol, vitamin E is actually a family of vitamins made up of four tocotrienols and four tocopherols. Most research has focused on d-alpha tocopherol, and this is the form commonly found in supplements. But research indicates that tocotrienols are even more important for cardiovascular health, as well as for providing protection against cancer and other degenerative diseases.

Tocotrienols have a different molecular structure than tocopherols, and it’s their unique structure that provides them better access to cells. Within the cells, tocotrienols provide enhanced antioxidant protection and activate gene signals, including the regulation of cholesterol. Research shows that tocotrienols have up to 60 times more powerful antioxidant properties in lipid biological systems than alpha-tocopherol.⁴⁰ In addition, cellular uptake of tocotrienols is up to 70 times higher, as its distinct chemical structure readily allows rapid absorption by body cells and organs.⁴¹

In the past couple of decades, tocotrienols have been shown to be powerfully effective in protecting the cardiovascular system, including normalizing cholesterol levels and maintaining artery health. Research shows that tocotrienols reduce the rate at which the liver synthesizes cholesterol, resulting in lower levels of total and LDL cholesterol. In April 1991, the American Journal of Clinical Nutrition published research demonstrating that tocotrienols reduced cholesterol levels in pigs with inherited high cholesterol, with an astonishing 44 percent drop in total cholesterol and a 60 percent decrease for LDL.⁴²

Researchers have subsequently found that tocotrienols help lower plasma cholesterol levels by blocking the HMG-CoA reductase enzyme. This enzyme is one of the primary steps in producing cholesterol, and blocking it effectively decreases serum cholesterol. In fact, the statin drugs used for lowering cholesterol work by inhibiting HMG-CoA reductase. However, where statin drugs work by clogging up enzyme receptors and blocking communication, tocotrienols effect a much gentler approach, working in harmony with the body to down regulate the enzyme.⁴³As a result, tocotrienols do not have the same negative side effects as do statins.

In a clinical trial of type 2 diabetics (who suffer progression of atherosclerosis more rapid than the general population, with 80% dying of an atherosclerotic event) researchers investigated the effects of tocotrienols on cholesterol profiles. After 60 days of treatment with tocotrienols, subjects showed an average decline of 23, 30, and 42% in serum total lipids, TC, and LDL-C, respectively. The researchers concluded that daily intake of tocotrienols by type 2 diabetics is useful in the prevention and treatment of hyperlipidemia and atherogenesis.⁴⁴ Animal studies show that tocotrienols not only reduce cholesterol levels, but also decrease lipid oxidation, which is a precursor to inflammation and artery damage.⁴⁵

In summary, I always recommend beginning with dietary and lifestyle changes to help lower and optimize cholesterol profiles. When additional help is needed, I turn to the botanicals and nutrients that provide gentle and effective support for normalizing cholesterol. With this comprehensive and holistic approach, I rarely find it necessary to resort to statin drugs.

 

References:

1. Man RY, Lynn EG, Cheung F, Tsang PS, O K. Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2). Mol Cell Biochem. 2002 Apr;233(1-2):153-8.
2. Journoud M. Jones PJH., Red yeast rice: A new hypolipidemic drug. Life Sciences. Vol. 74(22)(pp 2675-2683), 2004.)  J.H. Jones, Sch. of Dietetics and Hum. Nutrition, Fac. of Agric. And Environ. Sciences, McGill University, 111 Lakeshore Road, Montreal, QC H9X 3V9; Canada.
3. Bonovich, K, Colfer H, Davidson M, Dujovne C, Greenspan M, Karlberg R, et al. A Multi-Center, Self-Controlled Study of Cholestin In Subjects With Elevated Cholesterol. American Heart Association. 39th Annual Conference on Cardiovascular Disease Epidemiology and Prevention, Orlando, Fl. March 1999. \
4. Havel R. Dietary supplement or drug? The case of cholestin. Am J Clin Nut.r 1999;69(2):175-176.
5. 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;69:231-236.
6. Kuhn M, Winston D. Herbal Therapy and Supplements, A Scientific and Traditional Approach. Philadelphia, Pa: Lippincott; 2001.
7. Li C, Li Y, Hou Z. Toxicity study for Monascus purpureus (red yeast) extract. Information of the Chinese Pharmacology Society. 1995;12 (4):12
8. Li C, Zhu Y, Wang Y, Zhu J, Chang J, Kritchevsky D. Monascus Purpureus-Fermented Rice (Red Yeast Rice): A natural food product that lowers blood cholesterol In animal models of hypercholesterolemia. Nutrition Research. 1998;18(1):71-81.
9. 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;48:5220-5225.
10. Qin S, Zhang W, Qi P, Zhao M, Dong Z, Li Y , et al. Elderly patients with primary hyperlipidemia benefited from treatment with a Monacus purpureus rice preparation: A placebo-controlled, double-blind clinical trial. American Heart Association. 39th Annual conference on Cardiovascular Disease Epidemiology and Prevention, Orlando, Fl. March 1999. [Abstract]
11. Wang J, Lu Z, Chi J, Wang W, Su M, Kou W, 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):964-978.
12. Setnikar I, Senin P, Rovati LC. Antiatherosclerotic efficacy of policosanol, red yeast rice extract and astaxanthin in the rabbit. Arzneimittelforschung. 2005;55(6):312-7.
13. Lu Z, Kou W, Du B, Wu Y, Zhao S, Brusco OA, Morgan JM, Capuzzi DM; Chinese Coronary Secondary Prevention Study Group, Li S. 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 Jun 15;101(12):1689-93. Epub 2008 Apr 11.
14. Ye P, Lu ZL, Du BM, Chen Z, Wu YF, Yu XH, Zhao YC; CCSPS Investigators. Effect of xuezhikang on cardiovascular events and mortality in elderly patients with a history of myocardial infarction: a subgroup analysis of elderly subjects from the China Coronary Secondary Prevention Study. J Am Geriatr Soc. 2007 Jul;55(7):1015-22.
15. Li JJ, Lu ZL, Kou WR, Chen Z, Wu YF, Yu XH, Zhao YC; on behalf of the Chinese Coronary Secondary Prevention Study Group. J Clin Pharmacol. 2009 Aug;49(8):947-956. 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 Aug;49(8):947-956.
16. Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ, Li M, Iqbal N. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial. Mayo Clin Proc. 2008 Jul;83(7):758-64.
17. Bundy R., et al., Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomised double-blind placebo controlled trial. Phytomedicine (2008), doi:10.1016/j.phymed.2008.03.001
18. Dorn, M. (1995). Improvement in Raised Lipid Levels with Artichoke Juice (Cynara scolymus). Brit. J. Phytotherapy. 4(1);21-26.
19. Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic view. J Fam Pract. 2003 Jun;52(6):468-78.
20. Maros, T., Racz, G., Katonai, B., Kovacs, V.V. (1966). Effects of Cynara Scolymus extracts on the regeneration of rat liver. 1. Arzneimittelforschung 16(2):127-9.
21. Maros, T., Seres-Sturm, L., Racz, G., Rettegi, C., Kovacs, V.V. and Hints, M. (1968). Effect of Cynara scolymus-extracts on the regeneration of rat liver. 2. Arzneimittelforschung 18(7);884-6.
22. Samochowiec, L. et al. (1971). The influence of 1,5-dicaffeoylquinic acid on Serum Lipids in the Experimentally Alcoholised Rat. Panminerve Medica. 13;87.
23. Montini, M., Levoni, P., Ongaro, A., Pagani, G. (1975). Controlled application of cynarin in the treatment of hyperlipemic syndrome. Observations in 60 cases. Arzneimittelforschung 25(8):1311-4. Life Sci. 2004 Dec 31;76(7):775-82.
24. Lupattelli G, Marchesi S, Lombardini R, Roscini AR, Trinca F, Gemelli F, Vaudo G, Mannarino E. Artichoke juice improves endothelial function in hyperlipemia.
25. Pittler MH, Thompson CO, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev. 2002;(3):CD003335.
26. Gebhardt R. Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke extracts is reinforced by glucosidase pretreatment. Phytother Res. 2002 Jun;16(4):368-72.
27. Rondanelli M, Giacosa A, Opizzi A, Faliva MA, Sala P, Perna S, Riva A, Morazzoni P, Bombardelli E. Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. Int J Food Sci Nutr. 2013 Feb; 64(1):7-15. Epub 2012 Jun 29.
28. Wang X, Greilberger J, Ledinski G, Kager G, Paigen B, Jurgens G. The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis. 2004 Feb;172(2):239-46.
29. Stayrook KR, Bramlett KS, Savkur RS, Ficorilli J, Cook T, Christe ME, Michael LF, Burris TP. Regulation of carbohydrate metabolism by the farnesoid X receptor. Endocrinology. 2005 Mar;146(3):984-91. Epub 2004 Nov 24.
30. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent. Annu Rev Nutr. 2003;23:303-13. Epub 2003 Feb 26.
31. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 2002 May 31;296(5573):1703-6. Epub 2002 May 2.
32. Singh V, Kaul S, Chander R, Kapoor NK. Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. Pharmacol Res. 1990 Jan-Feb;22(1):37-44.
33. Verna SK and Bordia A, Effect of Commiphora mukul resin (gumguggul) in patients of hyperlipidemia with special reference to HDL. J Med. Res. 87: 356-60,1988
34. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther1994;8:659–664.
35. Szapary PO, Wolfe ML, Bloedon LT, Fair MB, Berezich DJ, Cirigliano AJ, Rader DJ. A double blind, randomised, placebo controlled clinical trial of standardized guggul extract in patients with hypercholesterolemia. Complement Ther Med 2002;10:–112.
36. Malhotra SC, Ahuja MMS. Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction ‘A’, ethyl-P-Chlorophenoxyisobutyrate and Ciba-13437-Su. Indian J Med Res1971;59:1621–1632.
37. Kuppurajan K, Rajagopalan SS, Koteswara Rao T, Sitaraman R. Effect of guggulu (Commiphora mukul–Engl) on serum, lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India1978;26:367–373.
38. Bordia A, Chuttani SK. Effect of gum guggulu on fibrinolysis and platelet adhesiveness in coronary heart disease. Indian J Med Res1979;70:992–996.
39. Wang X, Greilberger J, Ledinski G, Kager G, Paigen B, Jurgens G. The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis. 2004 Feb;172(2):239-46.
40. Serbinova E, Kagan V, Han D & Packer L. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha tocotrienol. Free Radic Biol Med 1991;10(5).
41. Saito Y, Yoshida Y, Nishio K, et al. Characterization of cellular uptake and distribution of vitamin E. Ann N Y Acad Sci 2004;1031.
42. Qureshi AA, Qureshi N, Hasler-Rapacz JO, Weber FE, Chaudhary V, Crenshaw TD, Gapor A, Ong AS, Chong YH, Peterson D, et al. Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias. Am J Clin Nutr.  1991 April 53(4 Suppl):1042S-1046S.
43. Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr. 2001 Feb;131(2):369s-73s.
44. Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. 2005 Oct;182(2):367-74.

Teoh MK, Chong JM, Mohamed J, Phang KS. Protection by tocotrienols against hypercholesterolaemia and atheroma. Med J Malaysia. 1994 Sep;49(3):255-62.