Cardiovascular Ingredients

As the biggest killer of both men and women in the United States, cardiovascular disease (CVD) is understandably a top consumer health concern. More than 71 million American adults suffer from at least one type of cardiovascular disease, according to the American Heart Association (AHA; Dallas), and in 2003, nearly 1 million people died from CVD.

The good news is that there’s growing evidence nutritional supplements can play a key role in treating people with heart disease. In the January/February 2006 issue of the Journal of Cardiovascular Nursing, Barry Kendler, a biology professor at Manhattan College (Riverdale, NY), examined a number of randomized, double-blind, placebo-controlled human studies to determine the importance of conditionally essential nutrients (CENs)-organic compounds the body usually produces in adequate amounts-in treating heart disease. Based on those studies, L-arginine, L-carnitine, propionyl-L-carnitine, and CoQ10 were classified as primary CENs; taurine was classified as a secondary CEN; and alpha lipoic acid, betaine, chondroitin sulfate, glutamine, and D-ribose were possible CENs. (Omega-3 fatty acids were not included in the review.)

“In view of the putative efficacy and safety of appropriate use of supplemental CENs, healthcare professionals need to familiarize themselves with . . . complementary therapy of CVD and share this knowledge with their patients and colleagues,” the article recommends.

For instance, the vasodilating effects of the heart-healthy ingredient Frutologic from BioSerae Laboratoires SA (Bram, France) may partly be attributed to its ability to enhance the activity of the CEN L-arginine, according to the company. Frutologic is available in a powdered form for beverages and a granulated form for tablets and capsules.

Another CEN, CoQ10, is available in a new formulation from Softgel Technologies Inc. (Los Angeles), which introduced CoQsol in January 2005. CoQsol-CF, a crystal-free version of the ingredient, is based on a unique formula that includes food-grade D-limonene and tocopherol. The formulation provides superior bioavailability by improving dissolution to enhance absorption.

“It has been the subject of some animal research and limited human studies, one of which was completed in January 2006 and is pending publication,” says Kenn Israel, director of marketing for Softgel. “There are a number of high-quality CoQ10s, but ours uses only natural ingredients. And animal studies have indicated that our specific formulation is preferentially taken up into more biologically active use sites in the body.”

In the meantime, consumers and manufacturers are exploring a variety of ingredients that research suggests may play a role in attacking heart disease both before and after it strikes.

PLANT STEROLS

The buzzword in cardiovascular ingredients at the moment is plant sterols, thanks to technological advancements and government approvals that have greatly expanded application possibilities. In 2000, the Food and Drug Administration (FDA; Rockville, MD) authorized the following coronary heart disease (CHD) claim for plant sterol and plant stanol esters: “Foods or beverages containing at least 0.4 g phytosterols, when consumed twice a day for a total intake of 0.8 g/day as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease.” In fact, more than 50 years of research on plant sterols, including a major 2003 study by the Mayo Clinic (Rochester, MN), has shown a reduction in average low-density lipoprotein (LDL) cholesterol of 8–15%, with no adverse effects.

“With over 50% of American households managing their cholesterol, there’s a huge opportunity for makers of functional foods and dietary supplements-if you have the right product,” says Laura Troha, Vegapure marketing manager for Cognis Nutrition & Health (La Grange, IL).

Until recently, plant sterols have only been designated generally recognized as safe (GRAS) for a fairly narrow range of applications, according to Steven Furcich, president of ADM Natural Health & Nutrition (Decatur, IL).

But in January 2006, FDA broadly expanded the GRAS categories of ADM’s CardioAid plant sterols to cover pasta and noodles; salty snacks; milk-type products and processed soups and puddings; soy milk, ice cream, and cream substitutes; adult confections; vegetarian meat analogs; cheese and cream; edible vegetable oil; ready-to-eat breakfast cereals; baked goods; and fruit and vegetable juices.

“This is probably the biggest event in sterols in several years,” says Furcich. “It’s really going to remove a big barrier to commercialization of sterols in the United States. It expands the category significantly, into areas where people have had interest previously, but did not have the ability to do it because of the GRAS status. No other sterol ingredient available today has been reviewed for so many new GRAS food categories.”

Furcich predicts that snacks, beverages, baked goods, and cereals will be the first categories to take advantage of CardioAid’s expanded GRAS approval, with new products appearing on supermarket shelves within the next two years.

The CardioAid lineup includes CardioAid phytosterols, CardioAid-S phytoesterol esters for foods, CardioAid-GA and CardioAid-M for low-fat or fat-free foods, and Cardio-Aid-WD for beverages.

“Sterols are a unique substance in nature with an extremely high melting point-over 300 º F,” says Furcich. “They’re very difficult to work with from an application standpoint, so we have a toolbox of solutions based around different food applications. And we have some new products we’ll be adding as well, from liquid applications like beverages to products like salty snacks.”

He adds that developing consumer awareness about plant sterols is the biggest challenge manufacturers face. ADM Natural Health & Nutrition has developed its own branding program for CardioAid, says Furcich, sampling about 800,000 consumers nationwide each year at events like marathons and women’s health shows.

Cognis Nutrition & Health, one of the world’s largest producers of phytosterols, has also embarked on a major consumer awareness campaign for its Vegapure line of natural plant sterol and sterol ester ingredients, which is being marketed to consumers under the new brand name Heart Choice.

“A new Web site, www.heart-choice.com, will allow consumers to find answers to frequently asked questions about cholesterol,” says Troha. “The Web site is being launched in conjunction with the Vitamin Shoppe’s introduction of its Heart Choice natural plant sterols dietary supplement. Cognis is also running advertisements in leading consumer health publications and on Health Centers Online, the leading Internet site for heart patient education.”

Cognis rolled out an expanded portfolio of Vegapure natural plant sterol and sterol ester ingredients last fall, including Vegapure FS, a free sterol ground powder for tablets and functional foods, along with three nongenetically modified, identity-preserved sterol and sterol ester products developed for tablets, softgels, two-piece hard shells, and functional foods. And in July, the company opened a new $25-million high-performance facility in Illertissen, Germany, to boost capacity for producing sterol esters and Tonalin CLA for body composition.

“This state-of-the-art facility means Cognis has an abundant supply of sterols and sterol esters,” explains Troha, adding that the company can tailor production according to precise formulation and manufacturing needs.

At Cargill Health & Food Technologies (Minneapolis), plans are also in the works for a broader range of consumer products incorporating the company’s Corowise plant sterols, says Pam Stauffer, marketing program manager.

“There’s a product in test market right now, and a couple of other new products that we hope will be coming out in this calendar year too,” says Stauffer. “We’re looking for more credible big brands to add to the roster.”

The most recent product launched with Corowise is Nature Valley’s Healthy Heart Chewy Granola Bars, which rolled out in August 2005 in Oatmeal Raisin and Honey Nut varieties. Each bar contains 0.4 g of plant sterols per serving, half of the recommended daily intake for heart health benefits.

B VITAMINS

Two new studies reported in the New England Journal of Medicine (NEJM) may have cast doubts over the effectiveness of some B vitamin supplements, but other recent studies suggest that the nutrients may still have a positive effect.

The Heart Outcomes Prevention Evaluation (HOPE-2) and Norwegian Vitamin Trial (NORVIT) studies, which were presented at the American College of Cardiology’s Annual Scientific Session in Atlanta on March 11 and published in the April 13 issue of NEJM, found that while vitamins B6, B12, and folate helped lower homocysteine levels, they did not offer protection against future cardiovascular events.

“While these studies contribute importantly to the research base, they have limited application for the general population,” says Annette Dickinson, PhD, consultant and past president of the Council for Responsible Nutrition (Washington, DC). “These studies did not test whether B vitamins used by healthy people can help keep them healthy. Instead, they looked at whether B vitamins can treat or reverse heart disease in people who already have it. Vitamins should never be expected to perform like drugs-their greatest promise is in prevention.”

Purple Reign

Thanks to a handful of creative marketers, the pomegranate is a hot commodity. Antioxidant-rich pomegranate juice is everywhere, from cookbooks to Men’s Health, which in February 2006 featured the Pomegranate Martini as the Drink of the Month.

The Pomegranate Express gathered steam in 2002, when several small studies identified the royal fruit’s health benefits. Exactly which combination of polyphenols and flavonoids is responsible for health benefits is currently being researched, according to PomElla marketer Geni Herbs (Noblesville, IN). For instance, results are expected soon from two human clinicals with PomElla regarding bioavailability and heart health.

The science indicates pomegranates have high antioxidant capabilities. Gencor Pacific (Anaheim, CA), supplier of Punicagen pomegranate extract standardized to 80% polyphenols, cites two studies conducted on pomegranate polyphenols that showed that they enhance the activity of endothelial nitric oxide synthase (ENOS) in the body, which acts on the nitric oxide pathway, increasing blood vessel dilatation and improving arterial health. Gencor soon will be starting a human clinical trial involving Punicagen. The studies were published in the May 2000 issue of the American Journal of Clinical Nutrition and the March 29, 2005, issue of the Proceedings of the National Academy of Sciences.

Meanwhile, the industry has discovered the royal fruit’s allure. PomWonderful (Los Angeles) grabbed the lion’s share of the market by making pomegranate juice fun. Mainstream companies have begun following Pom’s lead. SoBe Beverages (Norwalk, CT) recently announced SoBe Life Water vitamin-C and -E enhanced water beverages. One of the flavors-Pomegranate Cherry.

According to David Madsen, director of scientific affairs for Pharmavite (Mission Hills, CA), new research on thiamin, a water-soluble B-complex vitamin, suggests that B vitamins may indeed be helpful for some people.

Severe, prolonged thiamin deficiency has long been known to result in heart failure, but a new study suggests that thiamin deficiency is even more common among patients with congestive heart failure: The Journal of the American College of Cardiology reported in its January 17, 2006, issue that about one in three heart failure patients have deficient levels of thiamin. Researchers speculate that one reason may be the fact that heart failure increases the body’s need for certain nutrients, including thiamin. Because thiamin isn’t stored in the body, even those who follow a healthy diet may not get enough. In fact, even among the study’s control group, 12% of the subjects were found to be thiamin deficient, a percentage that Madsen calls surprising.

Diuretics are a major reason why people become thiamin deficient, Madsen says. “That’s why a multivitamin is good every day,” he explains. “Thiamin is among the safest of the essential nutrients-we’ve yet to find a dose at which there is any demonstrable toxicity of any kind.”

Niacin, more commonly referred to as vitamin B3, is another important player in heart health supplements because of its reported role in lowering cholesterol levels.

“Niacin has a long history, including numerous studies supporting use in maintaining cholesterol levels,” says Thomas J. Brancato, business and marketing manager for nutrition at Lonza Inc. (Allendale, NJ). “Niacin for use in supporting cholesterol levels is available both as a supplement and an FDA-approved prescription pharmaceutical. When taken at doses greater than the recommended daily intake, niacin works to maintain normal levels of the four key fractions: total cholesterol, LDL, high-density lipoprotein, and triglycerides.”

OMEGA-3s

The key omega-3 fatty acids include eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), both found mainly in oily cold-water fish, and alpha-linolenic acid (ALA), found mainly in dark green leafy vegetables, flaxseed oils, and some vegetable oils. Research has suggested heart health benefits for all three, but the omega-3s that come from fish tend to suffer from perception problems among consumers, according to new research analysis by Frost and Sullivan, which projects the omega-3 market to grow an average of 8% annually through 2010.

The report, titled “End-user Analysis of the Global Omega-3 PUFA Market,” suggests that omega-3 fish oils are thought to pass on a fishy taste and smell to their end products. Pronova Biocare (Lysaker, Norway), however, announced last fall that it had developed a unique process to deodorize its EPAX triglyceride (TG) oils so they are virtually odorless and tasteless.

“The deodorized omega-3 TG concentrates will bring new opportunities to our customers, enabling them to reach target groups focused on taste and smell,” says Anders-Morten Blindheim, director of the EPAX business unit. “We see particular advantages and new possibilities for applications where deodorized omega-3 oils are of major significance, including chewable capsules and liquid formulas.”

Flaxseed is one of the best sources of ALA, and recent studies suggest that ALA may have direct antiarrhythmic properties and may decrease the risk of sudden cardiac death, according to Julie Pizzey, West Coast sales manager for Pizzey’s Milling (Angusville, MB, Canada).

“Studies that have shown the benefits of consuming flaxseed include a dietary intervention study where individuals consuming a diet rich in ALA suffered significantly fewer nonfatal myocardial infarctions than those who followed a diet based on the Step 1 National Cholesterol Education diet,” Pizzey says. In another study, she adds, dietary intake of EPA and DHA was found to be not as significant in reducing secondary heart attacks as was ALA.

LOOKING AHEAD

As consumers continue to look for new ways to boost their heart health, research into new ingredients continues to be a priority in the marketplace. One up-and-comer is policosanol, a mixture of long-chain primary aliphatic saturated alcohols derived from the waxes of plants such as sugar cane and yams. Research on policosanol demonstrates that it may help maintain a normal range of existing cholesterol levels, according to Cyvex Nutrition (Irvine, CA), which supplies BioCosanol policosanol.

“As a branded product, BioCosanol policosanol from Cyvex Nutrition is a product consumers and manufacturers know and trust,” says Charlene Lee, Cyvex’s director of marketing and sales.

Another promising newcomer to the heart health market is UniBEX, containing patented bioactive compounds extracted from bamboo leaf, which was introduced by Unigen Pharmaceuticals Inc. (Lacey, WA) in late 2005. The bamboo leaf extract has demonstrated vascular repair activities, and its phenylpropanoids have been shown to be potent antioxidants in proprietary vascular research. Qi Jia, Unigen chief scientific officer, says data from a clinical study in Korea should be available by mid-2006, and that another clinical study will begin this year in North America.

“Unigen has spent the past five years developing UniBEX for its novel potential to address overall cardiovascular health and antioxidant activity, including healthy blood circulation and blood lipid profiles,” says Unigen president and COO Regan Miles.

Finally, another up-and-coming ingredient is Sytrinol, from Source One Global Partners (Chicago). According to Source One president and CEO Jesse Lopez, Sytrinol is a patented ingredient comprised of polymethoxylated flavones and tocotrienols that has been shown to reduce LDL cholesterol by 27% and reduce triglycerides by 34%. Recently, Source One teamed up with Natural Factors (Coquitlam, BC, Canada) to launch Sytrinol in Canada. “Source One is extremely proud to be associated with Natural Factors,” says Lopez.