Controlling Cholesterol

References

The connection between cholesterol and heart health is being illuminated, even in mainstream health channels, with drug companies presenting useful factoids in their national ad spots. Take, for example, the commercial from Merck/Schering- Plough Pharmaceuticals that said cholesterol can come from “that cherry pie or your granddad Cy.” As suggested by the commercial, cholesterol levels are affected by both diet and genetics. While genetics are fixed—at least for the time being—diet is certainly adjustable, and there are numerous ingredients that can help consumers manage cholesterol naturally.

Cholesterol is a fat-like substance found naturally throughout the human body and, contrary to its villainous reputation, it actually performs some positive, necessary functions. For example, cholesterol plays a role in forming healthy cell membranes and participates in the formation of certain hormones.

Cholesterol is typically discussed in terms of “bad” and “good”: low-density lipoprotein (LDL) is the bad guy, while high-density lipoprotein (HDL) is the good guy. Together, these lipoproteins are responsible for transporting blood cholesterol to and from the cells. In combination with triglycerides (a form of fat produced in the body), LDL and HDL account for total cholesterol.

While some cholesterol is certainly necessary for health, the National Heart, Lung and Blood Institute National Institues of Health (NIH), noted total cholesterol over 200 mg/dL is considered borderline high, with 240 mg/dL the marker for “high” total cholesterol. In addition, individual lipids must be kept in balance. Levels of LDL between 130 and 159 mg/dL are considered borderline high; over 160 is high, and over 190 is very high. If LDL is too high or if it is oxidized, it can cause build-up inside the arteries, contributing to the formation of hard plaque, a condition known as atherosclerosis that increases the risk of heart attack and stroke. Similarly, the risk of heart attack and stroke increases when HDL levels are too low (40 mg/dL or less); HDL is believed to transport cholesterol back to the liver where it can be removed from the body.

The liver and other cells in the body produce about 75 percent of circulating cholesterol. The remaining 25 percent is consumed through the diet, which is why dietary changes are sometimes enough to manage cholesterol and protect against the No. 1 killer in America, coronary heart disease (CHD).

Fabulous Fiber

The American Heart Association (AHA) recommends fiber as part of a low-fat diet, specifically for lowering cholesterol and reducing the risk of heart disease.¹ Soluble fiber, according to AHA, lowers LDL cholesterol more effectively than a low-fat diet alone.

As a source of soluble fiber, oats and whole oat products were approved to bear a heart health claim by FDA in 1995 due to the body of research supporting their benefit. Adding 35 to 50 g/d of oat bran to a fat-modified diet for four weeks significantly lowered total and LDL cholesterol in 235 hypercholesterolemic men, according to a 2003 German study.² A 2005 Canadian study showed 28 g/d of oat bran significantly raised HDL cholesterol and lowered the ratio of total:HDL cholesterol in 34 premenopausal women after four weeks.³

Oat beta-glucan, a concentrated fermentable fiber, has shown promise in cholesterol management. Consuming 6 g/d of oat betaglucan (as OatVantage™, from GTC Nutrition) significantly lowered total and LDL cholesterol in 75 hypercholesterolemic subjects in a study at the University of Minnesota, St. Paul.⁴ Similarly, a Venezuelan study showed 6 g/d of oat beta-glucan (as Nutrim™, from FutureCeuticals) added to the AHA Step II diet was significantly more effective than the diet alone for lowering LDL cholesterol in 38 men with mild to moderate hypercholesterolemia.⁵ Oat beta-glucan appears to act by reducing cholesterol absorption.⁶

Like oat bran, barley contains soluble fiber and has been approved for the FDA heart health claim since 2005. In fact, replacing 20 percent of carbohydrate calories with barley effectively lowered total and LDL cholesterol in 18 men with moderately elevated cholesterol.⁷ LDL and total cholesterol also drop significantly with the addition of 3 g/d or 5 g/d of barley beta-glucan (as Barliv™ barley beta-glucan, from Cargill), according to a randomized, controlled study out the University of Minnesota, Minneapolis.⁸ After six weeks, subjects receiving 5 g/d of high- and low-molecular weight treatments experienced 15-percent and 13-percent reductions in LDL cholesterol, respectively, and subjects in the 3 g/d groups exhibited reductions of 13 percent and 9 percent.

Another type of fiber that may lend itself well to cholesterol management is cactus fiber. A 2006 French study of 68 overweight women showed 1.6 g of dehydrated cactus leaves (Opuntia ficus indica, as NeoPuntia®, from Bio Serae) with each meal increased HDL cholesterol and reduced triglycerides.⁹ What’s more, at the end of the six-week study, 39 percent of the treatment group, compared to 8 percent of the control group, were no longer considered to have metabolic syndrome, a significant risk factor for developing type 2 diabetes.

Rice bran fiber concentrates also appear to positively affect cholesterol.¹⁰ Researchers at Advanced Medical Research in Madison, Wis., treated type 1 and type 2 diabetic patients and found the fiber concentrate reduced hyperlipidemia in both groups.

Protein Power

Soy protein has been shown in animal and clinical trials to lower triglycerides, total and LDL cholesterol, as well as increase HDL cholesterol. According to scientists from the Banting Research Centre in Ottawa, Ontario, there are numerous mechanisms of action at work, including the fact that both soy and its isoflavones alter the gene expression involved in lipolysis (fat metabolism).¹¹

Contrary to the Canadian findings, a Chinese study published in September 2007 showed neither 40 mg/d nor 80 mg/d of soyderived isoflavones affected lipid profiles during one year of study.¹² However, a meta-analysis of 11 studies published in the April 2007 American Journal of Clinical Nutrition indicated soy isoflavones significantly decreased total and LDL cholesterol in healthy and hypercholesterolemic subjects, although more dramatically in those with already high cholesterol.¹³

Like soy, hydrolyzed whey protein can lower LDL cholesterol, and may be a good first line of cardiovascular treatment in hypertensive patients, according to researchers at the University of Minnesota at Minneapolis.¹⁴ For six weeks, 30 hypertensive patients were randomized to receive 20 g/d of hydrolyzed whey protein (treatment) or unmodified whey protein (control). At the end of the study, LDL levels were improved in the treatment versus control group.

Fabulous Fats

Unlike fiber and protein, fat is not generally recognized as “healthy,” and should be eaten in moderation as part of a hearthealthy diet. Limiting fat intake is important for managing cholesterol, but so is eating the right kinds of fats. The essential fatty acids (EFAs) are a group of good fats that protect heart health by increasing HDL cholesterol and decreasing triglycerides. For example, the long-chain polyunsaturated fatty acids (LCPUFAs) found in fish are known to improve cholesterol profiles, according to a study of 923 pregnant women at the Swedish Medical Center in Seattle.¹⁵ Women who reported eating fish twice or more per week had lower triglycerides and higher HDL than women who reported eating fish only once or less per week. Additionally, the women who ate more fish had higher red blood cell concentrations of total LC-PUFAs, specifically the omega-3 eicosapentaenoic acid (EPA).

EPA and docosahexaenoic acid (DHA) are so effective for reducing triglycerides, FDA approved a prescription form of the omega-3s for the purpose of regulating lipid levels, with therapeutic dosages being 2 to 4 g/d of EPA and DHA, according to researchers at Virginia Commonwealth University in Richmond.¹⁶ They added the treatment may also increase LDL levels, but the net effect is a reduction in non-HDL cholesterol.

A policosanol omega-3 nanodispersion (as Nanocosanol®, from Valensa) may lower all parameters of cholesterol—except HDL, which may increase slightly—when taken in a twice-daily 690 mg capsule (containing 10 mg of policosanol and 100 mg of omega-3s), according to a company-sponsored trial reported in 2006.¹⁷ In a three-month, non-controlled, open-label trial, the most clearly established changes among the 11 subjects were in total cholesterol, and the LDL:HDL and total:HDL ratios.

Policosanol, a waxy substance derived from sugarcane, is independently recognized for its ability to reduce LDL and total cholesterol. In a study comparing policosanol to statin therapy, researchers at the Medical Surgical Research Center in Havana City, Cuba, reported while the statin was more effective for lowering LDL and total cholesterol, policosanol had significant effects on both in patients with type 2 diabetes.¹⁸ Furthermore, policosanol was more effective at increasing HDL cholesterol levels.

Krill oil may be even more potent than fish oil for managing cholesterol levels, according to the December 2004 issue of Alternative Medicine Review.¹⁹ Researchers at McGill University in Montreal conducted a multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up, and found 1 to 3 g/d of krill oil (as Neptune Krill Oil™, from Neptune Technologies and Bioressources) was more effective for reducing total cholesterol, triglycerides and LDL, as well as increasing HDL, than either 3 g/d of fish oil (180 mg/g EPA and 120 mg/g DHA) or placebo.

A vegetarian source of PUFAs and a rich source of lignans, flaxseed oil is also established in the literature for improving cholesterol levels. A high-fat animal model reported in 2006 compared PUFAs (flax and trout), monounsaturated fatty acids (MUFAs, as peanut) and saturated fat (as chicken skin), and showed flax was the most beneficial for lowering cholesterol.²⁰

Omega-3s from fish oil esterified to plant sterols (as CardiaBeat™, from Enzymotec) may be more helpful for improving heart health than fish oil alone, or olive oil or sunflower oil esters of plant sterols, ac cording to Canadian researc h.²¹ Researchers recruited 21 moderately overweight, hyperlipidemic subjects for the semirandomized, single-blind, four-period crossover study, which compared four diets, each containing 30 percent of energy as fat, 70 percent of which was from extra virgin olive oil and the remainder from one of four supplements: olive oil (OO), fish oil (FO), fish-oil fatty acid esters of plant sterols (FO-PS), or sunflower oil esters of plant sterols (SO-PS). Both sterol diets lowered LDL cholesterol and the total:HDL ratio, although FO-PS was more effective for increasing HDL levels. A subsequent study appearing in the October 2007 Lipids in Health and Disease indicated FO-PS (as CardiaBeat) also decreased fasting and post-prandial triglycerides.²²

Independently, plant sterols are well known for their cholesterollowering properties, particularly when incorporated in fatty foods, according to researchers at University of California, Sacramento.²³ The placebo-controlled October 2006 study showed fatty food isn’t necessarily a requirement, as subjects given 1 g of plant sterols in 240 mL of reduced-calorie juice twice daily for eight weeks exhibited significant reductions in total and LDL cholesterol and increases in HDL cholesterol. A similar study, utilizing a low-fat cocoa snack food enriched with 1.5 g of phytosterols, showed similar results; the treatment group exhibited reductions in total and LDL cholesterol and the ratio of total:HDL cholesterol compared to placebo.²⁴

To investigate whether plant sterol esters in capsule form were as effective as food-based plant sterols, researchers at East Tennessee State University, Johnson City, conducted a double blind, placebocontrolled, sequential study with a four-week placebo phase followed by a two-week wash-out period and a four-week treatment phase.²⁵ During the treatment phase, 16 subjects with high cholesterol took 1.3 g/d of plant sterol esters (as Vegapure® Natural Plant Sterol Esters, from Cognis) in capsule form. Compared to the placebo group, those in the treatment group exhibited significant reductions in LDL, total:HDL and LDL:HDL ratios, as well as increases in HDL.

Total cholesterol can be improved with conjugated linolenic acid (CLA), which has potent anti-atherosclerotic properties, according to a Polish study in the August 2007 British Journal of Nutrition.²⁶ The study showed CLA-enriched eggs (containing cis-9,trans-11 and t-10,c-12 isomers) significantly reduced total cholesterol and atherosclerotic plaque size in an animal model of atherosclerosis.

Awesome Antioxidants

Atherosclerosis can also be prevented by protecting LDL particles from oxidation, or lipid peroxidation. The omega-9 olive oil is known to prevent lipid oxidation, as well as fortify the body’s overall antioxidant levels, according to researchers at the Institute of Protein Biochemistry, CNR Via Marconi, in Naples.²⁷ Similar to olive oil, flavonoid polyphenols extracted from olive leaf (Olea europaea L.) bolster antioxidant levels, as noted by the Naples researchers. Their study showed both oleuropein and hydroxytyrosol inhibited LDL oxidation in vivo, and worked synergistically to “anticipate” oxidation and prevent it.

Cocoa is another natural antioxidant that has been promoted as a hear t-healthy ingredient because of its ability to improve cholesterol, according to researchers at Harvard University, Boston.²⁸ They reviewed 136 studies and concluded cocoa’s benefit lies partially in its ability to increase HDL and decrease LDL oxidation.

Chocolate enriched with plant sterols and stanols (as Reducol™, from Forbes Medi-Tech) is more effective than non-enriched chocolate for reducing cholesterol, according to a 2002 study.²⁹ After four weeks, those in the treatment group exhibited significant reductions in plasma total (6.4 percent) and LDL cholesterol (10.3 percent).

Garlic is believed to inhibit hepatic cholesterol synthesis as a mechanism of action, according to a 2001 report from researchers at Complutense University in Madrid, Spain.³⁰ Their 16-week animal study showed aged garlic extract (as Kyolic®, from Wakunaga) prevented diet-induced high cholesterol. In a pilot trial of aged garlic extract (as Kyolic), researchers at Harbor-UCLA Medical Center Research and Education Institute in Torrance, Calif., found the extract slowed the rate of coronary calcification.³¹ Garlic may also prevent the oxidation of LDL par ticles, and therefore atherosclerosis, according to a review published in the March 2001Journal of Nutrition.³²

A study published in the same issue of the Journal of Nutrition indicated it may be the saponins derived from garlic that are responsible for its cholesterol-lowering effects.³³ The study involved an animal model of high cholesterol and showed garlic saponins lowered total and LDL cholesterol without affecting HDL cholesterol.

LDL cholesterol, as well as triglycerides, can be significantly decreased with a proprietary combination of Phellodendron amurense and orange peel extracts (as Flavoxine®, from Next Pharmaceuticals), as demonstrated in a company-sponsored, double blind, placebo-controlled trial.³⁴ The combo was also shown to increase HDL cholesterol.

Citrus bioflavonoids and palm tocotrienols have each been shown in animal research to lower total cholesterol.³⁵ Researchers at SourceOne Global Partners conducted two open-label studies and one double blind study, where subjects were randomized to receive either 270 mg citrus flavonoids plus 30 mg tocotrienols (as Sytrinol®, a combination of PMFsource™ Citrus Bioflavonoids and TocoSource™ Palm Tocotrienols) or placebo daily for a period of four weeks (groups 1 and 2) or 12 weeks (group 3). Subjects receiving the antioxidant combo showed significant reductions in total cholesterol (20 percent to 30 percent), LDL (19 percent to 27 percent) and triglycerides (24 percent to 34 percent).

LDL cholesterol is also affected by a class of plant compounds called polyphenols, which includes the anthocyanins found in brightly colored berries. Heart patients who were given anthocyanin-rich pomegranate juice, exhibited significant reductions in LDL cholesterol and LDL oxidation after one year, and even more so after three years.³⁶ The patients who drank pomegranate juice every day also showed reductions in intima-media thickness, a measure of atherosclerosis development based on the accumulation of foam cells in the intima of the artery.

Grape polyphenols, which include anthocyanins, may lower triglycerides and very low-density lipoprotein (VLDL) concentrations in spite of a high-cholesterol diet, according to animal research conducted at the University of Connecticut, Storrs.³⁷ Researchers concluded the polyphenols altered cholesterol metabolism in the liver, which affected VLDL secretion rates.

Grape seed extract (GSE) may be a means of preventing arteriosclerosis, according to a Japanese trial published in the April 2007 Journal of Nutritional Science and Vitaminology.³⁸ Researchers came to this conclusion after their 12-week study showed GSE (containing 200 mg or 400 mg of proanthocyanidins) reduced LDL oxidation.

A June 2007 study featured in Obesity indicated green tea extract, which is rich in the polyphenol subcategory of catechins, is another promising antioxidant for protecting against cardiovascular disease.³⁹ After a two-week diet run-in period, researchers conducted a 12- week, double blind, parallel, multicenter trial, where subjects were given green tea with 583 mg/d (n=123) or 96 mg/d (n=117) of catechins. Subjects in the high-catechin group showed greater reductions in body weight, blood pressure and LDL cholesterol than the lowcatechin group.

Green tea acts through reduced liver cholesterol concentrations by increasing the efflux of cholesterol from liver cells, according to an Australian study published in the July 2007 Lipids.⁴⁰ Their animal study failed to show a decrease in LDL cholesterol with green tea, but did show a significant increase in HDL cholesterol.

HDL cholesterol can also be increased with Pycnogenol®, as noted in the October 2002 issue of Lipids.⁴¹ Researchers at the University of California, Sacramento, gave 25 healthy subjects 150 mg/d of Pycnogenol for six weeks and saw significant increases in HDL, as well as reductions in LDL, in two-thirds of the subjects.

The carotenoid lycopene is also known for its antioxidant activity as a method of improving heart health, and was shown to significantly decrease lipid peroxidation in 40 hypertensive patients who ate tomatoes for 60 days.⁴² In vitro research with lycopene showed that it reduced macrophage foam cell formation (which would help prevent atherosclerosis) by decreasing lipid synthesis.⁴³

Another carotenoid, the marine antioxidant astaxanthin, may contribute to the prevention of atherosclerosis by inhibiting LDL oxidation time.⁴⁴ Subsequent research showed 50 mg/kg/d of astaxanthin oil significantly decreased triglycerides and increased HDL in a rat model of metabolic syndrome.⁴⁵ In an unpublished, company-sponsored trial, 4 mg/d of astaxanthin (as BioAstin®, from Cyanotech) decreased total and LDL cholesterol by 17 percent and triglycerides by 24 percent after 30 days.⁴⁶

Additional animal research with astaxanthin compared it to vitamin E (as alpha-tocopherol) for its ability to prevent complications related to atherosclerosis.⁴⁷ Researchers at Linköping University in Sweden found both antioxidants improved atherosclerotic plaque stability, which lowered the risk of rupture and subsequent clot formation.

Vital Vitamins

A study of alpha-tocopherol in combination with statin therapy, which appeared in the November 2007 American Journal of Health-System Pharmacy, showed while 400 IU/d increased serum alpha-tocopherol concentrations, it did not enhance the total- or LDL-lowering effect of the drug.⁴⁸ According to researchers at the Linus Pauling Institute in Corvallis, Ore., the vitamin E treatment resulted in a small but significant 6 percent decrease in HDL concentrations.

The reduction in HDL with vitamin E treatment may be due to genetic variables, according to animal research out of the Southwest Foundation for Biomedical Research in San Antonio, Texas.⁴⁹ Or, according to researchers at the University of California, Sacramento, the negative HDL impact is not attributable to vitamin E.⁵⁰ To prove it, they gave 127 patients with stable coronary artery disease 1,200 IU/d of vitamin E for two years, at the end of which, no negative changes in HDL were seen.

Alpha-tocopherol’s ability to reduce the risk of heart disease is well known, according to Australian researchers, although it might be equaled by another vitamin E isomer, gamma-tocopherol.⁵¹ Researchers conducted a five-week, placebo-controlled study and found 100 mg/d of gamma-tocopherol significantly reduced LDL cholesterol and platelet aggregation.

The tocotrienol isomers of vitamin E have been lauded in the literature for reducing the risk of atherosclerosis and lowering cholesterol levels.⁵² Gamma- and delta-tocotrienols appear to act like a sterol, creating a feedback mechanism that decreases the activity of HMG coA reductase (HMGR), the rate-limiting enzyme of cholesterol synthesis.⁵³ Tocotrienols are most abundant in palm, rice and annatto, ranging from 50 percent tocotrienols in rice to only desmethyl tocotrienols in annatto.

Clinical trials using annatto tocotrienol have reported positive results. In a two-month open study, daily supplementation with 75 mg annatto tocotrienol (approximately 67 mg delta-tocotrienol and 8 mg gammatocotrienol) reduced total cholesterol by 13 percent and LDL by up to 15 percent, and increased HDL by 4 to 7 percent.⁵⁴ Another four-week study found 100 mg/d annatto tocotrienol reduced total cholesterol by 15 to 22 percent and LDL by 10 to 20 percent.⁵⁵

Additional research suggests the vitamin E isomers may work best in combination.⁵⁶ That study showed a palm tocotrienol complex (33 percent alpha-tocopherol, 16.1 percent alpha-tocotrienol, 2.3 percent beta-tocotrienol, 32.2 percent gamma-tocotrienol, 16.1 percent deltatocotrienol, as Tocomin®, from Carotech) significantly lowered total cholesterol in an animal model of atherosclerosis, compared to tocopherol isomers or carotenoids, which did not change cholesterol much beyond the control diet.

Vitamin E can decrease markers of lipid peroxidation, but it needs vitamin C to perform at its full potential, according to a review in the January 2007 American Journal of Clinical Nutrition.⁵⁷ Combined treatment with 400 IU/d of vitamin E and 500 mg/d of vitamin C restored endothelial function after six months in children at risk of atherosclerosis.⁵⁸

Animal research reported in March 2007 showed high-dose vitamin C added to food (30 mg/100 g/d) significantly decreased total and LDL cholesterol and triglycerides, and increased HDL compared to a low dose (1 mg/100 g/d) when added to a high-fat diet.⁵⁹ Similar results were reported in December 2006, indicating vitamin C helps normalize lipid levels in an animal model of diabetes.⁶⁰ Another vitamin helpful for treating lipid disorders in diabetes is niacin.⁶¹ According to this review, niacin is unique because it can effectively treat all lipoprotein abnormalities, including reducing LDL and triglycerides, and increasing HDL.

Methods of increasing HDL cholesterol are becoming a more important subject of study, according to researchers at Tufts-New England Medical Center in Boston, due to a strong link between low HDL cholesterol and atherosclerosis.⁶² They added niacin has a “substantial” effect on raising HDL levels in addition to beneficially affecting total and LDL cholesterol and triglycerides. The broad effect niacin has on cholesterol is due to more than one mechanism of action, according to a November 2003 review by researchers at the Atherosclerosis Research Center at the University of California, Irvine.⁶³ Niacin inhibits diacylglycerol acyltransferase2 in the liver, which is involved in triglyceride formation. It also inhibits the apo AI catabolism pathway, which raises HDL.

Excellent Extras

Perhaps as well rounded as niacin, red yeast rice (Monascus purpureus cultivated on rice) has a widespread effect on cholesterol parameters: It significantly reduced LDL cholesterol, as well as the ratios of total:HDL and LDL:HDL cholesterol, as noted in a June 2007 study.⁶⁴ Researchers at the University of Tromso in Norway conducted a meta-analysis of red yeast rice and found it significantly lowered LDL and total cholesterol, and raised HDL cholesterol compared to placebo.⁶⁵ The investigation of 93 randomized, controlled trials showed the supplement has therapeutic effects similar to numerous statin drugs with no serious side effects.

Another agent popular in Asia for lowering cholesterol, guggul (Commiphora mukul), is becoming more popular in the United States, according to researchers at the University of Pennsylvania School of Medicine, Philadelphia.⁶⁶ Based on previous findings that the guggulsterones in guggul can inhibit cholesterol metabolism, researchers conducted a double blind study to investigate. They randomly assigned 103 adults with high cholesterol to take 1,000 mg or 2,000 mg of Gugulipid® from Sabinsa or placebo three times daily. After eight weeks, participants in the treatment groups exhibited small increases in LDL cholesterol, while those in the placebo group showed a small decrease.

A 2003 research review in Nutrafoods discussed this study and stated that a secondary review of the information showed a small but statistically significant reduction in fasting triglycerides in patients with elevated LDL at baseline.⁶⁷ And, subjects taking the higher dose also exhibited lower oxidized LDL after adjustment.

A combination of fenugreek seed powder, guar gum and wheat bran (as FiberNat, from Asian Herbex) also has an impact on LDL oxidation, as noted in the January 2007 Molecular and Cellular Biochemistry.⁶⁸ The animal study showed the supplement not only increased lag time to LDL oxidation, but also decreased maximum LDL oxidation and LDL oxidation rate. Additional research with fenugreek seed extract showed it decreases triglycerides in animals on a high-fat diet, according to a 2005 Japanese study.⁶⁹

The many facets of cholesterol management, from lipid peroxidation to lipid ratios, offer food for thought on keeping a healthy balance. “High cholesterol is one of the major controllable risk factors for coronary heart disease, heart attack and stroke,” according to AHA. With all the natural ways to improve cholesterol, formulators have a full arsenal of dietary weapons to offer against coronary heart disease, the No. 1 killer in America.

Kimberly J. Retzlaff is a Denver-based freelance writer and former managing editor of Natural Products INSIDER.

References

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