Cardiovascular Health: Take Heart

September 9, 2010
Jennifer Grebow
Jennifer Grebow

Jennifer Grebow is editor-in-chief of Nutritional Outlook.

It’s a fact often repeated: Heart disease is still the leading killer in the United States. The good news is that there are drugs and natural aids that can help consumers fight some of the mechanisms of heart disease, such as high cholesterol and high blood pressure.

It’s a fact often repeated: Heart disease is still the leading killer in the United States.

Death rates from cardiovascular disease may have declined (by 29.2%, from 1996 to 2006, according to the American Heart Association’s 2010 Heart Disease and Stroke Statistics report). But the burden of disease remains high. In 2006, cardiovascular disease still accounted for 1 out of every 2.9 deaths in the United States. Nearly 2300 Americans die from cardiovascular disease daily. That’s one death every 38 seconds. If you think that sounds scary, you’re right.

The good news is that there are drugs and natural aids that can help consumers fight some of the mechanisms of heart disease, such as high cholesterol and high blood pressure. As consumers increasingly look to natural remedies, cardio health has become a leading category in dietary supplements. Those concerned with the side effects associated with pharmaceuticals, such as statin drugs for cholesterol, are looking to heart-health supplements.

“Consumer awareness of the problems associated with statin drugs is fairly widespread, and many are looking for safe and effective natural alternatives,” says Steve Holtby, president and CEO of Soft Gel Technologies Inc. (Los Angeles).

Dietary supplements are not necessarily viewed as replacements for pharmaceuticals. “Cardio nutraceuticals do not compete with cardio drugs,” says Matt Phillips, president of Cyvex Nutrition (Irvine, CA), which offers its BioVin grape-extract line. “Hopefully, by taking cardio nutraceuticals, you can prevent or delay the symptoms or health issues that require one to take cardio drugs.”

“Ultimately,” he says, “I think they are complementary.”

In fact, it’s pharmaceutical advertising that may be driving consumer awareness of the dangers of heart disease-and the need to take care.

“Much success begins with mainstream-triggered awareness,” says Dean Mosca, president of Proprietary Nutritionals Inc. (PNI; Kearny, NJ). “In the case of heart health, television is abundant with commercials for pharmaceuticals that lower cholesterol. Bayer Aspirin exhorts viewers to take one a day to prevent heart attacks. Therefore, the overall mindset is that heart health is a priority for adult men and women.”

“The fear of a heart attack-‘the big one’-remains the most constant boogeyman among American adults,” he adds.

Even the drug industry may be taking a second look at the benefits a natural approach can provide. GlaxoSmithKline markets its new Lovaza omega-3-based triglyceride-lowering medication as “where nature meets science.”

“The success of Lovaza has also increased the market for [omega-3] supplements,” says Baldur Hjaltason, business development and sales manager for omega-3 supplier EPAX AS (Aalesund, Norway). He predicts more omega-3 prescription drugs will hit the market in the near future-possibly combining statins and omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

In the supplements sphere, old- and new-guard ingredients offer health benefits, each taking a different approach to cardiovascular health. A few are discussed, below.

 

Phytosterols

Phytosterols and their role in cholesterol lowering have been well documented. The Food and Drug Administration (FDA), the American Heart Association, and the U.S. National Cholesterol Education program endorse the use of these ingredients. FDA allows such health claims as “Two grams of free sterols may lower low-density lipoprotein (LDL) cholesterol levels.”

Naturally present in vegetables, fruits, vegetable oils, legumes, nuts, and grains, plant sterols have a molecular structure similar to cholesterol. “Our body can only absorb cholesterol, and not much of the plant sterols,” says Laura Troha, marketing manager for Cognis Nutrition and Health (La Grange, IL), which offers its Heart Choice plant sterols. “Because of this unique difference, dietary plant sterols compete with cholesterol, thus blocking the absorption of dietary cholesterol in the bloodstream.”

Cognis says numerous clinical studies have shown that when used synergistically with statin drugs, Heart Choice can lower cholesterol by a further 8 to 15%-good news for those seeking to lower cholesterol by natural methods.

On average, people consume between 0.15 to 0.25 g of phytosterols per day from their normal diet, according to Corazonas, a line of snack foods infused with phytosterols. Vegetarians may consume more, between 0.3 and 0.4 g per day. However, FDA states that people need to consume at least 0.8 g daily to begin seeing benefits-which is where supplementation can help.

In the past decade, phytosterols have played a greater role in functional foods-primarily in spreads and dairy products. In recent years, they have begun expanding to a wider range of food types as well.

Ramona Cappello, whose Corazonas brand utilizes Archer Daniel Midland’s (Decatur, IL) CardioAid plant sterols, says, “Some people with borderline high cholesterol who don’t necessarily need medication yet can also take small steps like replacing their old snack foods with Corazonas snacks that provide enjoyment in snacking but can help lower bad cholesterol, too.”

“Diet changes will not always completely solve a high-cholesterol problem, but it can be a good complement to prescription medications,” she adds.

Consumers may agree, as Corazonas products, including tortilla and potato chips, have seen business grow well and are now rolling out nationwide to mainstream retailers like Costco.

Clinical studies have shown the benefits of phytosterols in food. A study published in October 2008 in Lipids in Health and Diseaseexamined the cholesterol-lowering effects of Cognis’s Heart Choice in a 200-ml soy beverage containing 2.6 g of the ingredient. The randomized, placebo-controlled, double-blind study involved 50 subjects and found that regular consumption of the beverage for eight weeks significantly reduced total, non-high-density lipoprotein (HDL), and LDL cholesterol.

A study published in July in the American Journal of Clinical Nutritionexamined the effect of a high dose (9 g) of plant stanols in food on LDL cholesterol. The researchers found that the dose, consumed daily, could effectively lower LDL cholesterol by as much as 17.4%.

Cognis says that product development with Heart Choice is expanding to pasta and salad dressing. New Novel Foods approval in Canada now also opens doors for the ingredient in food there.

 

Omega-3

Recommended by the American Heart Association, omega-3 has been steadily building awareness with consumers for heart health. Research indicates that fish oil omega-3s can support cardio health in numerous ways-by decreasing triglyceride levels and reducing plaque buildup (atherosclerosis) and inflammation of the arteries, among others.

Science increasingly pairs fish oil omega-3 with heart-health benefits. “The greatest number of scientific papers are associated with heart health, and that is reflected in the fact that more than half of consumers link fish oil–derived omega-3 fatty acids with heart-health benefits,” says EPAX’s Hjaltason.

For cardio health, EPAX offers its 6000TG supplement, which contains 33% EPA and 22% DHA. “Due to the high interest in the cardio-protective area, this product is the best-selling single EPAX item, growing [in] double digits every year,” says Hjaltason.

Alpha-linolenic acid (ALA) omega-3 from plant sources is also being promoted as a heart-health supporter. At the Institute of Food Technologists’ (IFT) Annual Meeting and Food Expo in July, Cargill introduced Clear Valley Omega-3 Oil. A patent-pending blend of oil from canola seed and flaxseed providing a minimum of 160 mg of ALA per serving, the oil is designed to be a “drop-in” oil replacement for many food applications. Cargill markets it as a way for food manufacturers to easily improve a food’s heart-health profile.

“This is not a small opportunity for our customers,” said Cargill’s vice president of oils and shortenings, Willie Loh, PhD, in a press release. “Seventy-seven percent of consumers have used heart-healthy foods in the past year, and 63% of consumers are trying to add sources of omega-3 to their diets.”

Also at the IFT show, Solae (St. Louis) demonstrated applications for Soymega, which it calls “the world’s first omega-3 soybean oil with stearidonic acid.” At the show, attendees were able to taste salad dressing featuring Soymega, which the company says is currently being evaluated by numerous food companies. Solae says that stearidonic acid is unique because it converts to EPA more efficiently than ALA does in humans.

Promoting an ideal balance of omega-3 and omega-6 is currently an industry focus, says Holtby of Soft Gel Technologies, which offers its EZ Mega 3. While omega-6 tends to be plentiful in people, due to its availability through plant oils used for cooking, omega-3 is typically lacking. A typical ratio of omega-6 to omega-3 in the body can be as high as 30:1. Holtby says that a few studies suggest that a lower ratio of omega-6 to omega-3, in the ballpark of 5:1 or 2:1, may be effective in reducing risk of heart disease.

Another area of interest may be combining omega-3 with other heart-healthy ingredients. This approach may offer benefits beyond what omega-3 alone provides, according to Israel-based supplier Enzymotec. A few years ago, Enzymotec introduced a patented, proprietary ingredient that combines omega-3 DHA and EPA with phytosterols. A 12-week, double-blind, randomized, controlled study funded by Enzymotec and published online in July in Cardiovascular Drugs and Therapydetermined that n-3-phytosterol esters helped lower triglycerides significantly (19%) in patients (91 subjects, minus 24 drop-outs) with mixed hyperlipidemia-without causing an increase in LDL cholesterol levels. Researchers also noted a reduction in blood pressure and inflammation markers.1

Omega-3 from all sources continues to expand its presence in functional foods. Both Clear Valley Omega-3 and Soymega are such examples. Jennifer Kibel, senior account executive at Denomega Nutritional Oils (Sarpsborg, Norway), says that the company’s shelf-stable, water-soluble form of omega-3 powder, derived from cod and salmon, is increasingly making its way into instant and powdered applications such as soups, beverages, cereals, and baking mixes.

 

Fiber

Fiber has long been touted as a heart-healthy ingredient. In March, Stratum Nutrition (St. Charles, MO) introduced Artinia, a combination of soluble fiber (1,3 beta-glucan) and insoluble fiber (chitin) targeting the oxidation of LDL cholesterol. The ingredient is a naturally occurring component of the cell wall of the fungus Aspergillus niger.

Joseph Evans, PhD, Stratum’s manager of pharmacology, says the company recently initiated a significant clinical trial on Artinia. So far, a 28-day pilot study (single-blind, placebo-controlled) conducted by the University of Liège (Belgium) on 30 normocholesterolemic males concluded that Artinia may reduce the oxidation of LDL cholesterol by approximately 26%.2 

“Artinia is significant for cardiovascular health because it enhances the body’s natural defenses against the damaging effects of reactive molecules and has been reported to lower oxidized LDL cholesterol in humans,” says Evans.

“Other fibers have not been reported to have an effect on oxidized LDL cholesterol,” he adds. “Artinia is the only fiber that has been shown to reduce this oxidation biomarker for cardiovascular disease. Although not proven, this activity might be due to its unique structure compared to other fibers.”

The company sees possible applications in capsules, chewable tablets, smoothies, yogurt, and nutrition bars. “Because Artinia seems to promote the body’s natural antioxidant systems (e.g., superoxide dimutase and glutathione peroxidase), combining Artinia with other dietary antioxidants is attractive,” says Jeremy Moore, director of the company’s marketing and strategic development. “Additionally, Artinia supports healthy arteries that are already ‘clear,’ and it has a different mechanism than other ingredients for healthy blood flow, like vitamin K2 or nattokinase. So, these are also attractive potential combinations with Artinia.”

 

Nattokinase

Nattokinase is an enzyme derived from natto (soybeans fermented with Bacillus subtilis). Its ability to aid the heart lies in breaking down fibrin, a blood-clotting protein. When activated, fibrin forms fibrinogen, which is responsible for blood clotting-leading to angina, heart attack, and stroke.

Vesta Ingredients Inc. (Indianapolis), which supplies nattokinase, mentions a study performed jointly by JCR Pharmaceuticals (Kobe, Japan), Oklahoma State University, and Miyazaki Medical College on the effects of a 200-g dose of natto (food version) on 12 healthy Japanese subjects. Researchers found that natto was able to heighten the subjects’ ability to dissolve blood clots. On average, the subjects’ euglobulin lysis time (the period of time it takes to dissolve a blood clot) dropped 48%.

The company says that while doses of nattokinase can vary between 100 to 200 mg, benefits can be seen with a minimum 50-mg dose. “Nattokinase is able to complement medication already being taken for minor heart-health issues in a safe manner and is very similar to taking a 81-mg baby aspirin,” says Vesta’s Katherine Baron.

 

Red Yeast Rice

Red yeast rice may offer a range of heart-health benefits over statin drugs. Like statins, red yeast rice(Monascus purpureus)has been shown to lower cholesterol-most recently, in a 62-patient, 24-week, randomized, placebo-controlled study published in June 2009 in the Annals of Internal Medicine.3 The study found that red yeast rice, in addition to lifestyle changes, had a significant impact on hypercholesterolemia. The researchers concluded: “Red yeast rice and therapeutic lifestyle change decrease LDL cholesterol level without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.”

 “The divergences arguably strongly favor the use of red yeast rice over statin drugs under many circumstances,” says Dallas Clouatre, PhD, a Jarrow Formulas consultant.

He points to a study published in the American Journal of Therapeuticsthat showed an increase in diagnosis of diabetes and a lack of glycemic control in diabetes mellitus in patients taking high or long-term doses of statins.4 

“Just the opposite appears to be the case with red yeast rice extracts,” says Clouatre. “One recent Chinese study found that red yeast rice extract decreased insulin and blood glucose levels in a group of type 2 diabetics, meaning that there was better blood sugar regulation.5 This certainly is a point in favor of red yeast rice. Similarly, statins only marginally benefit HDL cholesterol, whereas compared with placebo, red yeast rice interventions improve HDL levels.”

 

Antioxidants

When it comes to the benefits of certain antioxidants for heart health, opinions vary.

 

CoQ10

Coenzyme Q10 (CoQ10) is vital to energy production in the body for functions such as keeping the heart pumping. “The growing body of scientific evidence and peer-reviewed clinical trials validates the many cardio-protective benefits of CoQ10,” says Jesse Lopez, president and CEO of CoQ10 specialist SourceOne Global Partners (Chicago). “The reduction of free radicals; improved function of the mitochondria; and increased energy, stamina, and cardio function are compelling examples.”

Studies have shown that CoQ10 may be present at lower levels in people with cardiac failure.6 In addition, clinical research has found that CoQ10 levels can be lower among those taking statin drugs.7.

Supplement companies like Jarrow Formulas (Los Angeles) have been exploring ways to combine ingredients targeting those looking for statin alternatives. The company markets a red yeast rice supplement that includes CoQ10. Those who want the positive effects of statins without a depletion of CoQ10 might look to such a natural, combined solution.

“We believe strongly in combining CoQ10 with other heart-healthy ingredients like omega-3, resveratrol, quercetin, curcumin, and polymethoxylated flavones (PMFs),” Lopez adds.

Once concern when shopping for CoQ10 is ensuring the ingredient’s efficacy. “Unfortunately, it is widely known that supplemented CoQ10 is poorly absorbed,” says Lopez. “To increase its beneficial effects, steps must be taken to improve absorption and bioavailability.” Lopez says that SourceOne uses a nanoemulsion system called VESIsorb to enhance the bioavailability of both its ubiquinone and ubiquinol forms of CoQ10.

Tocotrienols

E vitamins, including tocotrienols and tocopherols, may also play a role in heart health, although there has been scrutiny in recent years. Some companies, such as PNI, have stronger clinical evidence supporting vitamin E for cardiac function.

PNI’s Sytrinol ingredient for heart health comprises palm tocotrienols, as well as other antioxidants such as PMFs. Studies have shown Sytrinol to significantly lower total and LDL cholesterol, as well as triglycerides, and to increase HDL cholesterol.

The company says that Sytrinol’s PMFs nobiletin and tangeretin, derived from citrus fruit peels, are potent bioflavonoids that can decrease oxidation of LDL cholesterol. These PMFs lower levels of LDL cholesterol by preventing the manufacture of its building blocks, apolipoprotein B and triglycerides. (Apolipoprotein B is considered the primary building block of LDL cholesterol, present at almost 90%, while triglycerides are key contributors to the formation of apolipoprotein B.) Palm tocotrienols, the other main component in Sytrinol, are extracted from the fruit of the palm tree. They help control anti-inflammatory responses and degrade HMG-CoA reductase, a key enzyme in the body used by the liver to produce cholesterol.

Sytrinol’s most recent human clinical trial, a 12-week, placebo-controlled study published in the November/December 2007 (vol. 13, no. 6) issue of Alternative Therapies,assessed the cholesterol-reducing effects of Sytrinol’s ingredients (270 mg/day of PMFs and 30 mg/day of tocotrienols) on 120 patients with high cholesterol. The researchers concluded that daily treatment with Sytrinol caused significant reductions in total cholesterol (ranging from 20 to 30%), LDL cholesterol (19 to 27%), apolipoprotein B (21%), and triglycerides (24 to 34%).

BGG North America (Irvine, CA) also sees promise in tocotrienols for heart health. “Tocotrienols are really starting to gain recognition as the other half of the vitamin E equation,” says Chris Holland, vice president of sales and marketing.

He encourages companies to take a “full-spectrum” approach to tocotrienols. “Whether it’s justified or not, alpha-tocopherol has really taken a beating over the last several years. I think medical professionals and savvy consumers have questioned why they should only take alpha-tocopherol when there is so much research supporting the heart-health benefits of the other tocopherol isomers and tocotrienols. Alpha-tocopherol is only one of eight vitamin E isomers, and you’re missing all that mother nature has to offer unless you’re also getting the other tocopherol and tocotrienol isomers.”

He continues, “I believe full-spectrum vitamin E products will continue to grow and increasingly become the product of choice for consumers seeking a powerful cardio-support supplement.”

 

Resveratrol, Pycnogenol

Resveratrol is another ingredient being considered for its possible cardiac benefits. Last December, DSM Nutritional Products (Parsippany, NJ) presented the results of its first human clinical study on its resVida trans-resveratrol ingredient and its benefits to cardiovascular health-namely, blood vessel function. The double-blind, randomized, crossover intervention study was conducted on 19 hypertensive subjects. It found that compared with placebo, resVida significantly improved blood vessel function.

Healthy blood vessels are obviously a key factor to heart health. One factor that helps maintain vascular health is nitric oxide (NO), which is synthesized by cells lining blood vessel walls. NO’s interaction with a specific receptor on arterial smooth muscle helps relax the arterial muscle, resulting in increased vessel diameter-and better blood pressure. Synthesis of NO, however, can decline, which is where resveratrol can help by increasing NO synthesis.

Rob Kopala, president of BioArmor Labs Inc., a new dietary supplement company, chose resveratrol for his company’s HeartShield Alpha supplement for this reason. “Resveratrol has been found to increase the NO production of endothelial cells of arteries, which helps ‘relax’ the arterial lining, lowering a person’s risk of increased blood pressure and dangerous plaque formation. These benefits, combined with its potential as an anti-arrhythmic and an anti-inflammatory, show resveratrol’s promise as a multifunctional agent in regards to arterial and heart health.”

HeartShield Alpha also includes CoQ10 and a blend of phytosterols and phytostanols supplied by Forbes Medi-Tech Inc. (Vancouver, BC, Canada). “We chose a phytosterol and phytostanol mix based on data that long-term use of sterols alone had diminished effects,” explains Kopala. “When used with stanols, the long-term effect of phytosterols on lowering LDL cholesterol was maintained and even improved in those already on prescription cholesterol-lowering medications.”

Like resveratrol, Pycnogenol, French maritime pine bark, also helps increase NO synthesis. A two-week, double-blind, randomized, placebo-controlled study published in 2007 in Hypertension Researchconfirmed that Pycnogenol tablets (180 mg/day) improved circulation by increasing NO production and higher forearm blood flow by as much as 46%.8

Other clinical studies point to Pycnogenol’s positive effects on cardiovascular health, including reducing high blood pressure, normalizing blood platelet activity, strengthening capillary walls, and improving blood lipid profile.

 

Pterostilbene

An ingredient chemically related to resveratrol, pterostilbene may also pose cardio benefits. “We see pTeroPure as one of the novel, next-generation ingredients for heart health,” says Jeremy Bartos, PhD, ingredients product manager for pTeroPure (Irvine, CA), a nature-identical trans-pterostilbene ingredient (99% pure) introduced this March.

Like resveratrol, pterostilbene is found in small berries such as blueberries and grapes. “The main difference between pterostilbene and resveratrol is that pterostilbene contains two methoxy groups and one hydroxyl group, while resveratrol has three hydroxyl groups,” explains Bartos. “The two methoxy groups cause pterostilbene to be more lipophilic (oil-soluble) than resveratrol, which increases oral absorption and gives it a higher potential for cellular uptake.”

Unlike resveratrol, he says, pterostilbene activates peroxisome proliferator-activated receptors (PPAR), which decreases the body’s synthesis of triglycerides and very-low-density lipoprotein and helps regulate cholesterol levels.

Bartos says that the launch of pTeroPure may help bring pterostilbene back into heart-health discussions. “Pterostilbene is still relatively uncommon in the heart-health market; it gets most of its press for the antiaging market because it is closely related to resveratrol,” he says. “Pterostilbene got a decent amount of press back in 2004, when the first papers on its cholesterol-lowering benefits were published. But with no commercially viable source for pure pterostilbene at the time, the buzz faded. We are obviously hoping to change this with our clinical study on the effect of pterostilbene on lowering cholesterol and blood pressure.”

The study Bartos mentions is one the company is currently in the process of conducting, together with the University of Mississippi. Bartos says it will be the first human clinical trial on pterostilbene’s cholesterol- and blood pressure–lowering effects. Results of the 80-patient, randomized, double-blind, placebo-controlled intervention study (100 mg/day and 250 mg/day) should be released next year, he says.

Pterostilbene could be an ingredient to watch in the cardio-health sector in coming years-and one that the pharmaceutical industry may be watching as well. Bartos says that a hamster study published in May 2005 (vol. 4, no. 53: 3403-7) in the Journal of Agricultural and Food Chemistryshowed that pterostilbene outperformed the cholesterol-lowering drug ciprofibrate.

Cocoa Flavanols

In July, Mars Inc. (McLean, VA) announced a “first-of-its-kind” study published in the Journal of the American College of Cardiology that found that daily cocoa flavanol consumption can more than double the number of circulating angiogenic cells (CACs) in the blood.9 CACs help repair blood vessels and maintain healthy vessel function. Poor function of the blood vessels can lead to a range of cardiovascular diseases.

In the randomized, controlled, double-blind crossover study, 16 patients with coronary artery disease were given a low-flavanol-containing beverage (9 mg flavanols/serving), as well as a high-flavanol cocoa beverage containing 375 mg of cocoa flavanols (made with Mars’s Cocoapro process, which helps ensure a consistent flavanol level), twice daily, over 30 days. The study’s positive indications for flavanols in cardiovascular health make it a heart-health area to explore, said the researchers.

 

Focusing on Prevention

Above all, perhaps, what dietary supplements can do is turn the consumer mindset about managing heart health to preventive care. “Patients tend not to think about what they eat or maintaining an exercise regimen if they are on drug therapy for elevated cholesterol levels or heart disease and stroke,” posits Soft Gel Technologies’ Holtby.

Consuming beneficial dietary ingredients, whether from dietary supplements or the right foods, plus making lifestyle changes such as regular physical exercise, can make a difference in staving off alarming cardio conditions before they develop-and before applying the “quick fix” of a pharmaceutical. Consumers may be warming up to this approach.

“When consumers first begin to exhibit cardio problems, their primary care physician and/or cardiologist typically will admonish them to follow a new diet and change lifestyle behaviors, while prescribing drugs,” says PNI’s Mosca. “Most people are scared into submission and often foray their local natural-products stores or pharmacies with heavy supplement inventory.”

Stratum Nutrition’s Moore says that consumers become better educated all the time. “We believe awareness is high enough that consumers are beginning to look for specific heart-healthy benefits,” he says. “Our research indicates that the broad-based claim ‘supports heart health’ is still powerful, but specific claims such as ‘supports healthy cholesterol levels,’ ‘supports healthy blood pressure,’ and ‘supports healthy arteries’ have very strong consumer appeal and offer more differentiation in a market saturated with general cardiovascular claims.”

 

View references here

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