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Natural Approaches to HDL, LDL and Total Cholesterol

cholesterol artery graphic

Its that time of year when consumers buckle down and try to reduce. They want to cut calories, frivolous spending and bad habits. In the past, one of the yearly New Years goals may have been to reduce all forms of cholesterol; however, this is not the case anymore as the complexity of cholesterol is continually being explored in medical journals and doctors offices. Research has taught us the error of thinking that getting the numbers down is the only cholesterol goal. Not all cholesterol is unhealthy; in fact, some even need to work to balance their levels.

Cholesterol is a soft, waxy substance found in the bloodstream. It aids biological functions, such as the production of hormones, and is an essential component of cell membranes. Its measured in three ways: high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total. LDL cholesterol is known as the "bad" or lousy cholesterol. When too much of it circulates in the blood, it can clog arteries, increasing the risk of heart attack and stroke. LDL cholesterol is produced naturally by the body, but many peoples genes tell their bodies to make too much. Others cant blame their parents because diets rich in saturated fat, trans fats and dietary cholesterol also increase LDL levels.

HDL, termed good or healthy cholesterol, helps keep LDL cholesterol from getting lodged into artery walls. A healthy level of HDL may also protect against heart attack and stroke, while low levels of HDL (less than 40 mg/dL for men and less than 50 mg/dL for women) have been shown to increase the risk of heart disease.

Cholesterol is either made by the body or consumed from food. The liver and other cells make about 75 percent of blood cholesterol found in the human body; the other 25 percent comes from eating animal products. For many Americans102 million, according to the American Heart Associationtotal cholesterol is too high.

Consumers are starting to understand the differences between total, HDL and LDL, and learning how too much of one typeor not enough of anothercan put them at risk for coronary heart disease, heart attack or stroke. Cholesterol screenings measure levels of HDL and LDL. If HDL is too low or LDL is too high, health care professionals may prescribe getting regular physical activity, quitting smoking, reducing trans fat consumption and eating a balanced, nutritious diet. If those dont work, they may write a prescription for a statin, such as atorvastatin (Lipitor), simvastatin (Zocor) or rosuvastatin (Crestor).

Statins lower cholesterol by blocking the enzyme responsible for cholesterol production (3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGR) in the liver. Statins may also help the body reabsorb cholesterol that has built up in plaques on artery walls, preventing further blockage in blood vessels and heart attacks.

However, in blocking HMGR, statins also inhibit the production of other important intermediates downstream in the pathway, including coenzyme Q10 (CoQ10), dolichols, hemes and other proteins. Since these intermediates are inhibited by statins, many patients experience side effects ranging from myopathy to anemia and chronic fatigue syndrome, and even temporary memory loss. Patients on statins must also keep in mind most people take them for the rest of their lives. Side effects may be minor, but they could be there forever.

Those who use statins to manage cholesterol levels are often concerned with CoQ10 levels because it shares the biosynthetic pathway with cholesterol. CoQ10 is produced by the human body and is necessary for the basic functioning of cells. Statin usage is known to deplete CoQ10 levels,1 so supplementation is encouraged for those on these drugs. Healthy levels of CoQ10 can reduce the oxidation of LDL cholesterolthe first step in the formation of arterial plaque.2 Further, Italian research showed CoQ10 has a direct, antiatherogenic effect, and dietary supplementation with CoQ10 resulted in increased levels of ubiquinol10 within circulating lipoproteins and increased resistance of human LDL to lipid peroxidation.3

Tocotrienols also inhibit HMGRs cholesterol synthesis, but does it farther downstream in the process rather than by competitive inhibition. Tocotrienols are members of the vitamin E family and come in alpha, beta, gamma and delta forms. Vitamin E is also made up of four tocopherols (alpha, beta, gamma and delta). Tocotrienols are found in select vegetable oils, wheat germ, barley, saw palmetto, and certain types of nuts and grains.

Tocotrienols work differently than statins by dialing down cholesterol synthesis downstream in the process rather than by competitive inhibition. Unlike statins, American River Nutrition pilot studies showed CoQ10 levels increased by 20 percent when patients were taking 75 mg/d of its DeltaGold® tocopherol-free tocotrienol ingredient. Company studies have also shown 75 mg/d annatto tocotrienol/d decreased total cholesterol by 13 percent and LDL by 15 percent, while HDL levels showed a small, but insignificant increase.

In 1986, Asaf Qureshi at the University of Wisconsin isolated alpha-tocotrienol from barley and found it had cholesterol-lowering properties;4 later, he found delta- and gamma-tocotrienol were the most potent inhibitors of endogenous cholesterol synthesis of all tocotrienols,5 and tocopherol-free tocotrienol worked better in lipid reduction than tocopherol/tocotrienol mixtures.6

A 2006 chicken study on the tocotrienol-rich-fraction (TRF) of palm oil found it produced a dose-response (50 to 2,000 ppm) lowering of serum total and LDL cholesterol levels by 22 percent and 52 percent (P<0.05), respectively, compared with the control group.7 Alpha-tocopherol did not affect total or LDL-cholesterol levels, but supplemental alpha-tocotrienol within the 50 to 500 ppm range produced a dose-response lowering of total (17 percent) and LDL (33 percent) cholesterol levels. The more potent gamma and delta isomers yielded dose-response (50 to 2,000 ppm) reductions of serum total (32 percent) and LDL (66 percent) cholesterol levels. HDL cholesterol levels were minimally impacted by the tocotrienols; as a result, the HDL/LDL cholesterol ratios were markedly improved (123 to 150 percent). The researchers concluded the safe dose of various tocotrienols for human consumption might be 200 to 1,000 mg/d based on this study.

Qureshi also reviewed tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in 90 hypercholesterolemic human subjects and found a dose of 100 mg/d of TRF25, along with the AHA Step-1 diet, produced maximum decreases of 20 percent, 25 percent, 14 percent and 12 percent, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values.8

Both SourceOne Global and KGK Synergize Inc. combine palm tocotrienols with polymethoxylated flavones (PMFs) in product formulations. PMFs, one of the main active ingredients in Sytrinol® (manufactured by KGK Synergize Inc. and exclusively marketed by Proprietary Nutritionals), and PMF-Source (SourceOne Global), are a group of compounds derived from the peels of citrus fruits. The two most common are tangeretin and nobiletin, which are potent bioflavonoids. A study conducted by KGK Synergize Inc. found diets containing 1-percent PMFs significantly reduced serum total by 19 to 27 percent and very LDL by 32 to 40 percent.9 That study also found comparable reductions were achieved by feeding a 3-percent mixture of hesperidin and naringin (1:1, w/w), implying a lower potency of hesperidin/naringin versus PMFs.

PMFs were shown to have enhanced bioavailability when offered in soft gels (manufactured by Soft Gel Technologies Inc.) in a clinical trial. The company tested absorption rates of Sytrinol it soft gel form and found tangeretin and nobiletinwere four times more bioavailable compared to powder-filled, two-piece hard shell capsules. Further, the company said this form of Sytrinol was shown in several clinical trials to lower total cholesterol by 20 percent, LDL cholesterol by 22 percent and triglycerides by 28 percent.

Along with vitamin E, another letter vitamin, B3, aka niacin, has been shown to increase HDL cholesterol and decrease overall cholesterol when used in conjunction with statins.10 One unfortunate side effect of niacin is flushing, or warmth, tingling and itching of the skin. Flushing can range from minor warm or itchy facial skin to major body discomfort. However, flushing may be reduced by using a time-release formula.11

Dietary enzymes help to increase levels of HDL cholesterol, according to Triarcos research, which the company said was being prepared for publication at press time. It said a patented blend of digestive protease (as Aminogen®) added to whey protein significantly reduced the increase in LDL and total cholesterol levels seen when whey was consumed without Aminogen®. Aminogen® also increased levels of HDL cholesterol when added to that whey protein beverage.

From heat to sweet, policosanol is a cholesterol-lowering natural product derived from sugar-cane wax with a therapeutic range from 5 to 20 mg/d. Policosanol from honeybees wax or rice bran is also available on the market. Policosanol is a combination of long-chain fatty alcohols, including octacosanol, triacontanol, dotriacontanol, tetratriacontanol, hexacosanol, heptacosanol and nonacosanol. Several research studies showed policosanol from sugar cane is effective at reducing cholesterol levels. A 2002 study published in the American Heart Journal reviewed the literature on placebo-controlled lipid-lowering studies using policosanol, and found doses of 10 to 20 mg/d lowered cholesterol by 17 percent to 21 percent and LDL by 21 percent to 29 percent, and raised HDL by 8 percent to 15 percent.12 A year later, a clinical study compared policosanol to the statin drug lovastatin on 28 patients with intermittent claudication.13 Patients who took 10 mg/d of policosanol for 20 weeks experienced a 17.5-percent drop in total cholesterol, a 31-percent drop in LDL cholesterol, and a 31.5-percent rise in HDL cholesterol, while those who took 20 mg/d lovastatin reduced total cholesterol by 18 percent and LDL cholesterol by 22.6 percent. Five lovastatin patients, but none from the policosanol group, experienced adverse events.

Also from the plant cholesterol-lowering area, phytosterols (plant sterols) have attracted a great deal of interest for their effects on cardiovascular health, especially after FDA authorized a claim that allows phytosterol-enriched foods to assert they may reduce the risk of coronary heart disease (CHD) when combined with a diet low in cholesterol and saturated fats. Phytosterols are structurally similar to cholesterol, which makes them compete with cholesterol during absorption in the digestive tract, thereby lowering plasma cholesterol levels.14 According to one review, many clinical trials have proven plant sterols can effectively decrease high serum total and LDL cholesterol by reducing intestinal absorption of cholesterol.15 And an earlier review of 16 published human studies that used phytosterols to reduce plasma cholesterol levels in 590 subjects found phytosterol therapy was accompanied by an average 10-percent reduction in total cholesterol and 13-percent reduction in LDL cholesterol levels.16 Most recently, a 2010 study found daily consumption of plant stanols up to 9 g reduced serum LDL cholesterol concentrations up to 17.4 percent.17

Often combined with phytosterols, soy proteins have also shown to have cholesterol-lowering effects. A 12-week trial conducted by Metagenics showed a dietary program combining a low-glycemic index diet with a functional food delivering 30 g/d of soy protein and 4 g/d of phytosterols significantly decreased total cholesterol by 15.8 percent (P=0.0036) and LDL cholesterol by 14.8 percent (P=0.004) in postmenopausal women compared to subjects who followed the AHA Step 1 diet.18 In addition, significant improvements were observed in ratios of total to HDL cholesterol. That same soy protein/ phytosterol-fortified food, as part of a Mediterranean-style, low-glycemic-load diet improved cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia, including reductions in cholesterol, non-HDL cholesterol and cholesterol/HDL ratios (P<0.05).19

Beta-glucans are polysaccharides often found in traditional diets that feature in mushrooms, yeast, oats and barley. In 1997, FDA approved a health claim to be made for foods containing oat bran to be marketed as a cholesterol-reducing supplement at a dosage of 3 grams. A controlled, double blind study of 66 men who were randomly assigned to either oat milk (0.5-percent beta-glucan) or rice milk (control) for five weeks found oat milk significantly reduced serum total cholesterol (6 percent) and LDL cholesterol (6 percent) levels.20 Similarly, consuming at least 3 g/d of bioactive beta-glucan (from OatWell oat bran) may significantly lower LDL-cholesterol levels in individuals who have high cholesterol levels, according to a study that found two servings of OatWell cereal daily for four weeks decreased LDL cholesterol levels by 5.5 percent on average.21 Beta-glucan derived from barley was also found to lower cholesterol in mildly hyperchesterolemic men,22 and researchers from Jordan found barley and beta-glucan isolated from barley lowered total and LDL cholesterol concentrations by 0.3 mmol/l (P<0.00001) and 0.27 mmol/l (P<0.00001), respectively, compared with controls in a 2010 meta-anaylsis.23 And beta-glucan derived from yeast significantly reduced total cholesterol by 6 percent and LDL cholesterol by 8 percent in obese and hypercholesterolemic men in a 1999.24

Another glucan getting cholesterol-lowering attention is chitin-glucan, which is of fungal origin and is the main component of the cellular walls of Aspergillus niger. In combination with 1,3 beta-glucans, chitin-glucan (as ARTINIA by Stratum Nutrition) reduced oxidized LDL in healthy humans with normal cholesterol levels by 26 percent after four weeks, according to company studies. Additionally, the company said ARTINIA significantly decreased hypercholesterolemia in mice fed a high-fat diet, and a 13-week safety and toxicology study in healthy rats found ARTINIA produced no adverse effects at the highest dose administered (about 6.6 g/kg bodyweight). The European Food Safety Authority recently concluded ARTINIA is a safe food ingredient. Furthermore, to confirm the results of the initial clinical study, ARTINIA will soon be evaluated in a randomized, double blind, placebo-controlled, multi-center study in North America for beneficial effects on validated biomarkers of cardiovascular health and oxidative balance.

Ayurvedic medicine may not go the fungal route when it comes to cholesterol, but it has used guggul, the resin of mukul myrrh tree (Commiphora mukul), native to Arabia and India for more than 2,000 years to alleviate problems associated with blood lipid levels. A 1994 study of 61 patients (31 in the guggulipid group and 30 in the placebo group) found guggulipid, 50 mg twice daily for 24 weeks, decreased total cholesterol level by 11.7 percent, LDL cholesterol by 12.5 percent and the ratio of the total cholesterol to HDL cholesterol by 11.1 percent, whereas the cholesterol levels were unchanged in the placebo group.25 A Baylor College of Medicine, Houston, trial showed guggulsterone treatment decreased hepatic cholesterol in wild-type mice fed a high-cholesterol diet,26 and a study from Jackson Laboratory, Bar Harbor, ME, noted Commiphora mukul and its cholesterol-lowering component, guggulsterone, effectively inhibited LDL oxidation.27 A Massachusetts General Hospital meta-analysis of nine databases, 20 additional journals and bibliographies from 50 selected secondary references found scientific evidence suggested guggulipid elicits significant reductions in serum total cholesterol,28 and a Peninsula Medical School, Universities of Exeter and Plymouth, UK, analysis of 25 randomized clinical trials identified guggul as one of the 11 herbal medicinal products that have been most extensively studied and have demonstrated reductions in total serum cholesterol levels between 10 percent and 33 percent.29

Fish is a food item found in many traditional diets that has been shown to help reduce unhealthy cholesterol levels. Fish oil, rich in the omega-3 eicosapentaenoic acid (EPA), was as effective as statin drugs in reducing unhealthy cholesterol levels in hypercholesterolaemic patients in the large Japan EPA lipid intervention study (JELIS).30 Researchers examined more than 18,000 Japanese men with total cholesterol of 6.5 mmol/L between 1996 and 1999. Patients were randomly assigned to receive either 1,800 mg of EPA daily with statin (EPA group; n=9,326) or statin only (controls; n=9,319). At mean follow-up of 4.6 years, the researchers found a 19-percent relative reduction in major coronary events (P=0.011), with post-treatment LDL cholesterol concentrations decreasing by 25 percent, from 4.7 mmol/L in both groups. And not supplementing with fish oil may be detrimental to cholesterol management, as the GISSI-Prevention Study, a prospective randomized control trial of 11,000 patients with preexisting heart disease, found LDL cholesterol levels increased by 2.5 percent six months after patients were no longer receiving 850 mg of EPA and docosahexaenoic acid (DHA).31 With science like this, FDA allows supplements to claim supportive, but not conclusive research shows consumption of EPA and DHA omega-3 fatty acids may reduce the risk of CHD. Additionally, the agency ruled intakes of up to 3 g/d of marine omega-3 fatty acids are GRAS (generally recognized as safe), and the ruling included specific consideration of the reported effects of omega-3 fatty acids on LDL cholesterol.

Krill oil, another marine source of EPA and DHA, offers more omega-3s than a comparable amount of fish oil, which could be the reason a 2010 study found it significantly improved the HDL cholesterol/triglyceride ratio compared to fish oil.32 The study was performed by researchers at Akershus University College and University of Oslo, Norway, using Aker BioMarines Superba krill oil in healthy volunteers.

Omega-3s from plant sources, such as walnuts, are also effective treatments for cholesterol, according to a University of Barcelona, Spain, study.33 In the randomized, crossover trial, 49 men and women (mean age, 56 years) with polygenic hypercholesterolemia (a condition caused by a susceptible genotype aggravated by one or more factors, including excessive intake of saturated fat, trans fat, and cholesterol; obesity; and sedentary lifestyle) ate a Mediterranean diet or a diet of similar energy and fat content in which walnuts replaced approximately 35 percent of the energy obtained from monounsaturated fat for six weeks. Compared with the Mediterranean diet, the walnut diet decreased total cholesterol levels by 4.1 percent, LDL cholesterol levels by 5.9 percent and lipoprotein levels by 6.2 percent. Lipoproteins are molecules made of proteins and fat that carry cholesterol through the blood.

Similarly, the omega-3s in flaxseeds may be behind their ability to aid those with high cholesterol levels. Flaxseeds are one of the richest sources of alpha-linolenic acid (ALA) and lignans (a type of phytosterol), as well as a good source of soluble fiber. Human studies have shown flaxseed can modestly reduce serum total cholesterol and LDL cholesterol. In a double blind, randomized study, postmenopausal women who were not on hormone replacement therapy were instructed to consume 40 g/d of either ground flaxseed or wheat-based comparative control regimen for three months.34 Flaxseed supplementation lowered both serum total cholesterol and LDL cholesterol by 6 percent, whereas the comparative control regimen had no such effect.

And perhaps it was the omega-3s in the various nuts examined in a 2010 JAMA pooled analysis of data from 25 trials that showed consuming them was associated with improvements in blood cholesterol levels.35 Joan Sabaté, M.D., of Loma Linda University, Loma Linda, CA, and colleagues pooled primary data from trials conducted in seven countries and involving 583 women and men with high cholesterol or normal cholesterol levels. All the studies compared a control group to a group assigned to consume nuts; participants were not taking lipid-lowering medications. Participants in the trials consumed an average of 67 g/d (about 2.4 ounces) of nuts. This was associated with an average 5.1-percent reduction in total cholesterol concentration, a 7.4-percent reduction in LDL cholesterol and an 8.3-percent change in ratio of LDL cholesterol to HDL cholesterol.

Nuts and fish are dietary staples much like rice is, and all three can help naturally address cholesterol issues. Red yeast rice is produced by fermentation of rice using the fungus Monascus purpureus. It produces active compounds that inhibit HMGR. A study published in the American Journal of Clinical Nutrition found healthy subjects (46 men and 37 women aged 34 to 78 years) with hyperlipidemia who were not being treated with lipid-lowering drugs and received 2,400 mg/d of red yeast rice containing, by weight, 0.4 percent HMGR inhibitor, had a significant reduction of total cholesterol (16 percent) and LDL cholesterol (22 percent) after 12 weeks of treatment, as compared to placebo.36

While not historically known for being part of healthy diet, chocolate has made its debut into the healthy natural ingredient spotlight, due in part to its ability to lower cholesterol levels in individuals at risk for heart disease. A Chinese study found cocoa, when consumed in moderate amounts providing 260 mg of polyphenolsantioxidants found in fruits, vegetables and chocolatecan lower both total cholesterol and LDL levels by about 6 mg/dL.37 Researchers reviewed eight trials (involving 215 participants) and focused on short-term data to evaluate the effects of cocoa on plasma lipid. Cocoa consumption significantly lowered LDL cholesterol by 5.87 mg/dL (P<0.05) and marginally lowered total cholesterol by 5.82 mg/dL (P =0.08). However, no significant change was seen in LDL cholesterol in high-quality studies (three studies included; -4.98 mg/dL; P=0.23). Subgroup analyses suggested a cholesterol-lowering effect only in those subjects who consumed a low dose of cocoa and with cardiovascular disease (CVD) risks.

For those who would rather have a cup of tea than hot chocolate, they may want to choose yerba maté to boost cholesterol health. The plant has been used for centuries by native South Americans to reduce stress, increase energy and focus, and encourage a sense of well being. Its rich variety of polyphenols is thought to be beneficial for a number of human health issues, including protecting HDL and LDL from oxidation. A group of researchers from Touro University, Vallejo, CA, investigated whether the polyphenol-rich beverage, obtained from extract of Ilex paraguariensis (IP), prevented the loss of paraoxonase 1 (PON-1), an antioxidant enzyme carried mainly by HDL that offers cardioprotective effects.38 Healthy volunteers drank either 0.5 L of IP extract, 0.5 L of coffee and milk or nothing. PON-1 activity increased an average of 10 percent above the changes seen in the coffee and milk group (P<0.05). The authors said, In conclusion, we demonstrate that IP extract may, to some extent, prevent the loss of the antiatherogenic function of HDL afforded by PON-1 when the particle is under oxidant stress. A review of yerba maté tea conducted in 2007 by the University of Illinois noted the beverage has been shown to be hypocholesterolemic, to protect DNA from oxidation and in vitro LDL lipoperoxidation, and to have a high antioxidant capacity.39

Coffee is another breakfast beverage that may reduce levels of oxidized cholesterol. According to research from FutureCeuticals, a single serving of ingredients produced using a proprietary technology from the whole fruit of the coffee plant, Coffea Arabica (as CoffeeBerry®), may stimulate the activity of a human blood enzyme associated with maintenance of healthy cholesterol levels; the company said the ingredient has also been shown to possibly reduce levels of oxidized LDL cholesterol. The company also noted an independent expert panel recently affirmed the GRAS status of its CoffeeBerry products, including CoffeeBerry Whole Fruit Powder, Juice Concentrate Powder and Forte Soluble Concentrate.

Whether in a beverage, a food fortified with soy protein or a supplement of PMFs, nutritional product formulators have a lot of options to help consumers meet their cholesterol goals in 2011. These natural ingredients, along with a healthy diet and exercise, can help raise the good and reduce the bad, which is what were all looking for this time of year.

 

References are on the next page...

References for Natural Approaches to HDL, LDL and Total Cholesterol

1.       Mortensen SA, et al. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18 Suppl:S137-44.

2.       Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992 Jun 26;1126(3):247-54.

3.       Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007 Sep;37(1):31-7.

4.       Qureshi AA, et al. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem. 1986 Aug 15;261(23):10544-50.

5.       Pearce BC, et al. Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem. 1992 Oct 2;35(20):3595-606.

6.       Qureshi AA, et al. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). Am J Clin Nutr. 1991 Apr;53(4 Suppl):1021S-1026S.

7.       Yu SG,  et al. Dose-response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens. Lipids. 2006 May;41(5):453-61.

8.       Qureshi AA, et al. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis. 2002 Mar;161(1):199-207.

9.       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.

10.   Ceska R, et al. [Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: non-pharmacological and pharmacological approaches]. [Article in Czech] Vnitr Lek. 2010 Jul;56(7):647-54.

11.   Norris RB. Flush-free niacin: dietary supplement may be benefit-free. Prev Cardiol. 2006 Winter;9(1):64-5.

12.   Gouni-Berthold I, Berthold HK.  Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J. 2002 Feb;143(2):356-65.

13.   Castaño G, et al. Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Angiology. 2003 Jan;54(1):25-38.

14.   Heinemann T, Axtmann G, von Bergmann K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest. 1993 Dec;23(12):827-31.

15.   Reiner Z, Tedeschi-Reiner E. [The effects of plant sterols on hypercholesterolemia] [Article in Croatian] Lijec Vjesn. 2007 Aug-Sep;129(8-9):276-81.

16.   Ling WH, Jones PJ. Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci. 1995;57(3):195-206.

17.   Mensink RP, et al. Plant stanols dose-dependently decrease LDL-cholesterol concentrations, but not cholesterol-standardized fat-soluble antioxidant concentrations, at intakes up to 9 g/d. Am J Clin Nutr. 2010 Jul;92(1):24-33.

18.   Lukaczer D, et al. Effect of a low glycemic index diet with soy protein and phytosterols on CVD risk factors in postmenopausal women. Nutrition. 2006 Feb;22(2):104-13.

19.   Lerman RH, et al. Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial.  Nutr Metab (Lond). 2008 Nov 4;5:29.

20.   Onning G, et al. Consumption of oat milk for 5 weeks lowers serum cholesterol and LDL cholesterol in free-living men with moderate hypercholesterolemia. Ann Nutr Metab. 1999;43(5):301-9.

21.   Wolever TM, et al. Physicochemical properties of oat -glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial. Am J Clin Nutr. 2010 Oct;92(4):723-32. Epub 2010 Jul 21.

22.   McIntosh GH, et al. Barley and wheat foods: influence on plasma cholesterol concentrations in hypercholesterolemic men. Am J Clin Nutr. 1991 May;53(5):1205-9.

23.   Abumweis SS, Jew S, Ames NP. -glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials. Eur J Clin Nutr. 2010 Oct 6.

24.   Nicolosi R, et al. Plasma lipid changes after supplementation with beta-glucan fiber from yeast. Am J Clin Nutr. 1999 Aug;70(2):208-12.

25.   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 Ther. 1994 Aug;8(4):659-64.

26.   Urizar NL, et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 2002 May 31;296(5573):1703-6.

27.   Wang X, et al. The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis. 2004 Feb;172(2):239-46.

28.   Ulbricht C, et al. Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Complement Ther Med. 2005 Dec;13(4):279-90.

29.   Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic view. Fam Pract. 2003 Jun;52(6):468-78.

30.   Yokoyama M., et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8.

31.   [No authors listed] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55.

32.   Ulven SM, et al. Metabolic Effects of Krill Oil are Essentially Similar to Those of Fish Oil but at Lower Dose of EPA and DHA, in Healthy Volunteers. Lipids. 2010 Nov 2.

33.   Zambón D, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial. Ann Intern Med. 2000 Apr 4;132(7):538-46.

34.   Lucas EA et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in post-menopausal women. J Clin Endocrinol  Metab 2002; 87:1527

35.   Sabaté J, Oda K, Ros E. Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials. Arch Intern Med. 2010 May 10;170(9):821-7.

36.   Heber D., et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999 Feb;69(2):231-6.

37.   Jia L., et al Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2010 Jul;92(1):218-25.

38.   Menini T, et al. Protective action of Ilex paraguariensis extract against free radical inactivation of paraoxonase-1 in high-density lipoprotein. Planta Med. 2007 Sep;73(11):1141-7.

39.   Heck CI, de Mejia EG. Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci. 2007 Nov;72(9):R138-51.

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