Compounds from dietary fiber to plant sterols can beneficially impact serum cholesterol levels.

Photo by TJ Hine

Foodservices and grocery stores compete for "share of stomach" as they strive to provide the finite amount of food needed by consumers. Increasingly, pharmaceuticals, dietary supplements and foods battle for "share of healthcare" as consumers choose among options to treat a health condition. Nowhere is this more obvious than in controlling cholesterol.

Heart disease is the number one cause of death in American men and women with high cholesterol being a major risk factor. Nearly 100 million American adults are estimated to have borderline or high cholesterol, according to the American Heart Association (AHA). But consumers can "take heart." Options abound for lowering cholesterol through lifestyle, diet, supplements, and drugs.

Leveraging Lifestyles

Although total blood cholesterol is a good starting point to access health status, low-density lipoproteins ("bad cholesterol") are generally differentiated from high-density lipoproteins ("good cholesterol"). Smoking and other stresses tend to increase LDL and decrease HDL levels, while regular aerobic exercise is associated with lower LDL and higher HDL levels.

Excessive dietary saturated fat is the leading cause of elevated cholesterol. It fuels cholesterol production, and stalls its emission from the body. Unsaturated fat consumption enhances cholesterol elimination from the body, and its degradation into bile salts, lowering total cholesterol. (See diagram).

The AHA notes that genetics play a crucial role. Some individuals with unhealthy diets have low cholesterol while others eat properly and exercise, yet need medication to maintain cholesterol levels.

Population studies shed light on the impact of diet on cholesterol metabolism. Mediterranean and Asian populations show much lower incidence of elevated cholesterol and heart disease than many Western countries. Traditional diets of Mediterranean and Asian groups are high in fruits and vegetables and low in meats and saturated fats. The French population has been particularly intriguing. Their diet is high in butter and cream sauces, yet the incidence of heart disease is significantly lower than in other Western countries.

French Paradox and Flavonoids

Some say the French Paradox may be explained by looking at red wine consumption. Several studies show moderate alcohol consumption (one drink per day for women and two for men) can raise HDL levels. Research suggests that increased amounts of flavonoid antioxidants in red wine offer additional protection.

A preclinical study at the University of Scranton using normal and high cholesterol patients, who were given a standardized grape seed extract of 600 mg per day, found normal cholesterol patients had a 9.2% reduction in LDL cholesterol while high cholesterol patients had a drop of 12.3% in total cholesterol. The work was presented, at the National Meeting of the American Chemical Society, March 27, 2000 in San Francisco and will be given in full at the Pacifichem 2000 meeting December 15, 2000 in Hawaii.

Potential products for fortification with grape seed and red wine extracts include juice drinks, snack or health bars, yogurts, and cereals among others. "The extracts provide consistent amounts of polyphenols (flavonoids) that can be used for health maintenance or therapeutic purposes. It would take 1/4 to 1/3 pound of grapes to supply the same amount of flavanoids as 200 mg of grape seed extract," says Ron Martin, vice president North American sales for a supplier of grape seed extract products.

Green tea contains flavonoids called catechins. In one study, catechins lowered triglycerides and cholesterol in hamsters at doses equal to three cups of green tea per day.1 Chocolate also possesses flavonoids. (See page NS25 this issue of NutraSolutions.)

Daily Dietary Fiber

Both dietary soluble and insoluble fiber provide cardiovascular benefits. "Oatmeal's soluble fiber acts like sponges, soaking up cholesterol and carrying it out of the body. Numerous studies and an FDA claim back up these heart-health benefits," says Dr. Joseph Keenan, professor at the University of Minnesota Medical School. "The only other grain with equivalent cholesterol lowering ability is barley. Rye is probably somewhat effective. It has about 40% as much soluble fiber as oats but there aren't many studies using rye," says Keenan. A chief benefit of soluble fiber (in the form of beta glucan in oats) is that it almost exclusively lowers LDL with little impact on HDL. Also, the higher the LDL, the greater the effect. A medium-sized bowl of oatmeal (3 gms beta glucan) should lower the total and LDL cholesterol about 7-10%. In an uncontrolled trial in Lafayette, Colo., participants lowered, on average, 12% total cholesterol by eating a bowl of oatmeal a day, but may have added other lifestyle changes as well, such as exercise and a better diet.

Besides grains, beta-glucan is commercially available from yeast and a water insoluble version is derived from microbiological fermentation.

Chitosan, a dietary fiber from crustaceans, is a popular dietary aid to reduce total cholesterol and increase HDL/LDL ratios.2 "It is unique among carbohydrate polymers in that it tends to emulsify the oil in the stomach. Upon reaching the neutral conditions in the small intestine, it forms a gel with the fat, which inhibits physical access to the fat by lipases. This reduces fat absorption by the body," says Dave Angerer, director of R&D for a chitosan supplier.

Soy, Oils and Sterols

Soy protein can reduce cholesterol, particularly if it replaces animal protein.3 The Food and Drug Administration recently gave permission for health claims on products high in soy protein, indicating that these foods may help lower heart disease risk.

What contribution soy isoflavones may play in controlling cholesterol is still under investigation. A study published in the June 2000 issue of the American Journal of Clinical Nutrition showed soy isoflavones were able to lower LDL in even healthy younger women.4 Regular consumption of products containing plant sterols and stanols has shown total and LDL cholesterol reductions of 10% for sterol products and up to 14% for stanol-containing products. These compounds block cholesterol uptake from the digestive system, most likely through competitive absorption mechanisms.

Many studies have evaluated the benefits of stanols and sterols. A recent multicenter study conducted at the Cooper Institute in Dallas found that when patients taking statins, such as Lipitor or Pravachol, also used Benecol spread three times a day, they saw a signficant 17% further reduction in their LDL vs placebo—7%.

"Benecol, the only product available in the U.S. containing plant stanol esters, is easy to incorporate into daily meal planning since the spread can be used in cooking or baking," says Gilbert Leveille, WorldWide vice president for scientific and regulatory affairs at McNeil Consumer Healthcare, maker of Benecol Spread.

Fats play a positive role. In studies where people consume more fish oil and less saturated fat, LDL levels tend to decrease. However, when saturated fat intake remains constant and fish oil increases, LDL levels tend to remain the same or increase. The AHA supports eating fish regularly, but recommends fish oil supplements only under very specific conditions.

Most Americans don't eat enough fish to get the required amount of the omega 3 fatty acid docosahexaenoic acid (DHA). This troubling fact spurred research on enhancing cow's milk with DHA. DHA has shown potential for reduction in serum triglycerides and increases in HDL.5

Physician Fixes

Cholestin (patent pending) is a form of yeast (Monascus purpureus Went) fermented on rice. This traditional Chinese health food has been used for 2000 years. The effect of Cholestin is attributed to its presence of HMG-CoA reductase inhibitors, enzymes controlling cholesterol production in the liver. "Cholestin is not recommended as a replacement for drugs, however, it is tolerated much better than statin drugs. As a dietary supplement together with regular exercise and a healthy diet, Cholestin helps maintain healthy cholesterol levels," says Carsten R. Smidt, Ph.D., sr. director of pharmacology & clinical affairs at Pharmanex Inc.

Niacin (vitamin B3) is the most thoroughly researched vitamin for lowering cholesterol. Prior to today's cholesterol-lowering medications, it was the doctors' treatment of choice. It also has shown decreases in LDL and increases in HDL similar to that of certain statin drugs.

Vitamin E acts as an antioxidant by protecting LDL cholesterol from free radical damage. Studies show that LDL is even more likely to clog arteries when it is oxidized by free radicals as is caused by smoking. A recent survey of doctors6 found that vitamin E was the most common antioxidant vitamin taken by cardiologists, most often at 400 IU per day for protection from heart disease.

Prescribed pharmaceuticals, the statins are a group of cholesterol lowering drugs including Baycol, Lescol, Lipitor, Mevacor, Pravachol, and Zocor. Although expensive, these drugs can lower LDL by 25% or more. The FDA held discussions in July on whether to make certain statins available over the counter in lower doses. Despite the trend toward more OTCs, the decision was made to not proceed in this direction.

As long as this list of options appears, it still excludes other options. For example, an ayurvedic herb called Commiphora mukul that possess guggulsterones, compounds with molecular structures similar to soy isoflavones and cholesterol, is now appearing in dietary supplements. No matter how thorough its efficacy as backed by research studies, it must compete with oat bran to Lovastatin for its share of healthcare.

French Paradox Resolved with Resveratrol?

Recent studies point to anti-cancer and cardiovascular benefits of trans-resveratrol or "Res," an antioxidant found in certain foods such as nuts, raspberries and grape products. Now, a study published in Cancer Research's July 2000 issue hones in on Res molecular mechanisms and gives support to the health benefits of red wine.

A research team, including Minnie Holmes-McNary and Albert Baldwin Jr., at the University of North Carolina, Chapel Hill, finds that Res controls the activity of NF-kappa B, a protein that attaches to DNA in the cell nuclei to activate and deactivate certain genes. In particular, Res helps switch off this protective mechanism that prevent cancer cells from being destroyed by the body's natural defenses.

When Res was absent from cell culture systems, cancer cells survived. "But when Res was there under experimental conditions, we could successfully promote death of cancer cells by turning off NF-kappa B," says Holmes-McNary, one of the study's authors.

The research also applies to heart disease in that the scientists were able to also inhibit another NF-kappa B gene involved in inflammation and development of artherosclerosis.

Future research will extend to human subjects and will investigate the dosages required to provide these results.




On the Web: Cholesterol

www.nhlbi.nih.gov/chd
http://www.cholesterollowdown.org/
http://www.cholesterol.com/
http://www.benecol.com/
http://www.fda.gov/fdac/features/2000/300_soy.html#health%20
http://www.pharmanex.com