Tim Wright05.01.04
Cardiovascular disease, which includes heart disease and stroke, is the leading cause of death in the U.S. among men and women. Killing about 950,000 Americans each year, cardiovascular disease accounts for almost 50% of all deaths. The economic toll associated with cardiovascular disease is enormous, estimated at $351 billion last year, including $209 billion for healthcare expenditures, according to the Centers for Disease Control and Prevention (CDC), Atlanta, GA. As the baby boomers continue to age, cardiovascular disease will be a major issue, leading experts to predict that healthcare costs are only going to escalate, placing an even greater burden on an already fragile system.
Add to this the fact that consumers are becoming savvier about the negative side effects associated with pharmaceutical treatments, leading them to take preventative measures and seek natural alternatives, and it's hardly surprising then to find that the heart health category is one of the most dynamic areas of activity for both functional foods and dietary supplements.
Heart health is no longer just a "buzz word," according to Dan Murray, associate director-Nutrition, Lonza, Inc., Fair Lawn, NJ. "Most people now realize they are empowered to improve their heart health, extend their longevity and not simply perceive themselves as victims of their genetic make-up. This is a major development not only for the individual, but also for the healthcare system at large," he said. "Healthcare experts often talk about shifting the system from treatment to prevention, but few health concerns have the perceived payoff of cardiovascular care. Saving the system money may be a nice side effect, but living longer and living well is driving the individual effort on a daily basis."
Cardiovascular disease is not the consequence of a single isolated risk factor, but rather the end point of a complex process that starts early in life, according to Tova Arditi, scientific advisor, Solbar Plant Extracts, Ashdod, Israel. These include behavioral, environmental, socio-economic and genetic factors. "In order to prevent cardiovascular disease, it is necessary to simultaneously control the various risk factors and their determinants," he said. "Among the major risk factors are elevated blood lipids (cholesterol), diabetes, obesity and hypertension."
As heart disease is in part directly linked to diet, there are enormous opportunities for the natural products industry to formulate new heart healthy foods, beverages and supplements. Hartley Pond, technical sales manager, Van Drunen Farms, Santa Rosa, CA, offered his opinion on this opportunity. "Where the pharmaceutical industry tends to focus on people who are already sick with heart disease, the natural products and food industry has a great opportunity to develop foods and supplements that truly offer a strong level of prevention before we get sick," he said.
As the heart health category continues accelerating its growth, it is becoming more vast and multifaceted. Neil Sullivan, director of sales, Kyowa Hakko USA, New York, NY, said he believes the heart health category will be a good complement to the standard large volume vitamin, mineral and bone health markets. "The category is many-sided because there are multiple ways to address heart health," he said. "There are supplements available that have a direct impact on heart health. Likewise, there are supplements that support active lifestyles and weight loss, which indirectly support long-term heart health goals."
During the last few years there has been a proliferation of ingredients that have come out slated for cardiovascular health. Commenting on this trend was Scott Larkin, director of marketing, LycoRed-Biodar USA, New York, NY. "Cardiovascular health affects everybody. As a result, from a marking perspective, it is a big category with a lot of potential," he said. "Unlike a few years ago, consumers have grasped the concept of cardiovascular health. They're looking for answers, which makes it a good time to market into the category because the education is better. The companies we sell to look for new ingredients to get an edge. As a result, there have been a lot of new formulas introduced in both supplements, functional foods and beverages."
In terms of identifying indicators regarding heart health, Frank Assumma, director of marketing, Natural Health Science, Hillside, NJ, has noticed in the last two years that people have begun to look at the issue of heart health a little differently. "People are not looking at individual markers so simply anymore, such as high cholesterol levels, for example. What we've found in the last couple of years is that there are other factors that might be even better indicators and one of them is inflammation," he said. "There is more medical evidence on the role of inflammation in heart disease and more emphasis on inflammation related markers, such as C-reactive protein (CRP)."
Mr. Assumma continued, "We normally think of inflammation as something that happens around the joints, but it can happen within the bloodstream too. When platelets stick together and clog up arteries, the blood vessels become inflamed and as a result it makes the vessel narrower. The integrity of the vessels in the vascular system has become much more of an issue as it relates to heart health."
Much of the growth in the heart health category is being driven by the aging of the population and an increased incidence of obesity, both which are related to increased cardiovascular disease, according to Greg Stephens, vice president, sales and marketing, Nuture, Inc., Devon, PA. "Unfortunately from a public health perspective, the cardiovascular health market continues to grow as the U.S. population ages and becomes more obese. Outcomes from research have placed more emphasis on controlling insulinemic response for maintaining healthy cardiovascular function. Lower serum insulin levels lead to lower LDL levels. In addition, to control insulin levels one must also maintain lower levels of serum glucose, or blood sugar," he explained. "There also seems to be more of an emphasis on providing comprehensive management of cardiovascular disease through the management of controllable, related cardiovascular risk factors, including elevated cholesterol, elevated blood sugar, hypertension, obesity and smoking."
Heart healthy functional foods like bars, cereals, smoothies and shakes, breads and pastas have been flourishing over the past several years. The growth in the market for these types offunctional foods is proof that consumers are showing an increased interest in proactively managing their heart health in variety of ways. As a result, consumer packaged goods companies are looking for ways to improve the health profile of their foods and beverages, and heart healthy products are high on the list. According to Pam Stauffer, marketing manager, Cargill, Inc., Minneapolis, MN. "Evidence of this in the market include recent product launches, such as Minute Maid Premium Heart Wise orange juice, Rice Dream Heartwise rice milk and Lifetime lowfat cheeses.
Three major strategies are used in the marketing of functional foods for heart health, according Solbar's Mr. Arditi. "One strategy focuses on identifying the intrinsic benefits of existing components of the diet and leveraging these through nutrition marketing," he offered. "A quite different strategy focuses on identifying specific ingredients with heart health or cholesterol-lowering potential and adding these ingredients into a wide variety of foods-almost always foods in which the ingredients would not naturally be found in any significant quantities. And it is this strategy that has been the greatest focus of attention thus far for industry scientists, marketers and investors." Mr. Arditi said the third strategy is to exchange ingredients in foods that have been identified with an elevated risk for heart disease, for example, substituting the hydrogenated oils used in margarines and bakery products with plant stanols.
While the functional food segment seems like a good avenue of opportunity, something must be done from a regulatory perspective to facilitate innovation. Kyowa Hakko's Mr. Sullivan said it is the government's responsibility to raise the incentive for food companies to invest more within this category. "To motivate a majority of food companies to invest their money in the functional food category, a more relaxed regulation that gives the final product containing a proprietary ingredient a health claim could be one solution-similar to the Foods for Specified Health Uses (FOSHU) system in Japan," he said. "This system will enable the food companies to work on developing novel active compounds. The current framework allows only a limited number of commodity-type compounds to take advantage of the health claim regulation, and companies have to stick to those types of compounds if they want to use a health claim. This will limit both the category and the number of final products. What is worse, it will not motivate companies to discover new ingredients, which is a key driver necessary for the expansion of the functional food market."
A major factor propelling the heart health category forward is the increased level of consumer awareness. Part of the equation relates to consumers becoming much more knowledgeable about the negative side effects associated with the statin drugs, said Nurture's Mr. Stephens. "Even if nutritional interventions do not allow people to eliminate the use of statins, lowering the dose would impart a positive benefit. Over the past few years consumers have become more educated, focusing on lowering LDL," he said. "Connected to this is new research demonstrating that lowering LDL as much as possible has positive outcomes. For those with high cholesterol (>240mg/dL), consumers and medical professionals alike are looking to combine lifestyle modifications, including dietary changes, with pharmaceutical interventions, such as statin drugs."
Because the cardiovascular health category is so broad, it has the capability of supporting several products. The problem with that, Mr. Murray said, is consumer education has been so good that consumers have difficulty deciding which products to try and which ones to forego. "Daily supplement packs have done a nice job of meeting consumer needs both in delivering a variety of products and making the products convenient to use," he said. "However, most people still trust their healthcare provider to deliver information and treatments. Although today, they are more willing to ask questions of their healthcare provider rather than accept a standard treatment without explanation."
Natural Health Science's Mr. Assumma said the mass proliferation of products is not good for consumers because it creates confusion. "I think, like in most categories, there is just way too much information out there for consumers," he said. "Consumers who are knowledgeable and interested can pick up several journals or go online and get a lot of information, but there is almost too much information. Part of the problem in the category is that when you go to a pharmacy, drug store or just a regular health food store, it is very difficult to sort through the aisles and differentiate between products."
Lycopene. The image of the tomato is becoming synonymous with heart health, mostly because of large consumer ad campaigns, including that from Centrum. Lycopene is the main active constituent in tomatoes, which has been a recent focus in cardiovascular research. According to LycoRed's Mr. Larkin, lycopene has been shown to reduce hypertension and LDL cholesterol oxidation, both of which lead to plaque build-up in the arteries. LycoRed supplies Lyc-O-Mato, an all-natural extract of tomatoes standardized to contain 6% lycopene, in addition to a variety of other phytonutrients, including beta-carotene, tocopherols, phytosterols, phytoene and phytofluene.
When studied in relation to hypertension, a 250 mg daily dose of Lyc-O-Mato, which contains 15 mg of lycopene, was shown to reduce systolic blood pressure significantly. Another study found that Lyc-O-Mato protects LDL cholesterol from oxidative modification. In the study, Lyc-O-Mato made LDL cholesterol 90% more resistant to oxidation.
Mr. Larkin said that because of the clinical studies validating lycopene's effectiveness in supporting cardiovascular health, it is a hot ingredient that is in demand. However, he also said that while mainstream consumers are making the connection between tomatoes and heart health, they are not educated enough to know the difference between the natural and synthetic forms and are being misled. "The clinical studies in which lycopene was shown to reduce hypertension and LDL cholesterol were based on 15 mg of natural lycopene taken twice a day. There is only 300 mcg of synthetic lycopene in Centrum, which is not enough to experience heart health benefits," he said. "They're putting a synthetic splash in there just for label claim because lycopene is a hot ingredient. What we see coming from USP in the near future is that they're going to make companies identify on the label whether or not the lycopene contained within is a natural tomato extract or if it is synthetic lycopene. The challenge we face is getting consumers educated enough to look for natural tomato lycopene."
Soy Protein. Soy contains several different nutrients, however, the two that get the most attention are soy protein and soy isoflavones. Most research has focused on soy protein and since FDA approved a health claim in 1999 stating, "25 grams of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease," soy protein's popularity has really taken off in the heart health category.
In addition to soy protein's cholesterol-lowering properties, which most people are aware of because of the heart health claim, Geri Berdak, manager of public affairs, The Solae Company, St. Louis, MO, said that there are other factors that soy protein impacts to help reduce the risk of heart disease. "Soy protein has been shown to alter the way the liver metabolizes cholesterol, reducing it from the bloodstream," she said. "There has also been research conducted showing it helps arteries retain their elasticity."
Soy isoflavones also display similar cholesterol-lowering qualities, in addition to other heart health benefits, according to Jocelyn Mathern, technical specialist, Acatris, Inc., Minneapolis, MN. However, Ms. Mathern said, research has highlighted the synergism between both soy protein and soy isoflavones, which when taken together impart the most benefits. "Going back a few years, researchers wanted to know which, with regard to lowering cholesterol, was more beneficial-soy protein or soy isoflavones." she said. "The researchers fed a soy protein isolate with all of its naturally occurring isoflavones to one group of people and then they fed a soy protein isolate with its isoflavones removed to another group. The group that had consumed the soy protein isolate with its naturally occurring isoflavones had lower cholesterol levels, but the group that was fed the soy protein isolate without its isoflavones experienced no effect."
Kyowa Hakko was recently granted generally recognized as safe status (GRAS) by FDA for its newly developed soy peptide, CSPHP, an abbreviation for C-fraction soy protein hydrolysate with bound phospholipids, which may also play a role in promoting healthy cholesterol levels. Explaining CSPHP's mechanism of action was Mr. Sullivan. "CSPHP blocks cholesterol absorption at the intestinal level. It has a completely different mechanism than that of statin drugs," he said. "CSPHP works by interfering in the micelle formation, which is essential for cholesterol to be absorbed via the intestinal wall, and also by binding to the bile acid and pushing it out of the body."
CSPHP can be provided in tablet form or used as an ingredient in a wide range of food products. In fact, beverage products in Japan with formulations that include CSPHP have already been approved by Japan's Ministry of Health, Labor and Welfare (MHLW) as FOSHU, according to the company.
Plant sterols. Plant sterols have been shown in studies to reduce LDL cholesterol by 8-15%. "They are structurally similar to cholesterol and they compete with the cholesterol humans ingest for absorption through the small intestine," explained Cargill's Ms. Stauffer. Cargill's branded line of plant sterols, CoroWise, which are derived from natural grains including soy, corn and sunflower, recently received a lot of attention due to its inclusion in Minute Maid Premium Heart Wise orange juice.
Discussing plant sterols' mechanism of action, Ms. Stauffer said that the more phytosterols present in the intestine following a meal, the less cholesterol absorption will occur. In addition, she said, "The plant sterols that are consumed are not absorbed to any appreciable extent. When plant sterols are consumed, they not only inhibit the uptake of cholesterol by the body, but they are flushed through the system as well."
Grape Seed. The polyphenols found in grape seeds have received a lot of attention for their cardiovascular health properties. Ron Martin, vice president of sales, Polyphenolics, Inc., Granger, IN, said that the company has been doing a lot work with both its grape seed extract and grape pomace extract in the area of endothelial cell function. "Endothelial cells have to function properly or else arteriosclerosis will progress," he said. "We've done work to show that our grape seed extract and grape pomace extract were both effective in preventing hypertension and lowering cholesterol." Mr. Martin added that the company is about one and half to two years away from going after a qualified health claim, which it needs to obtain in order to expand into the food and beverage industry.
Researches using Italy-based Indena's grape seed extract, Leucoselect Phytosome, found that the ingredient protects easily oxidized LDL cholesterol under oxidative stress as observed in heavy smokers. This clinical study, conducted against placebo using the crossover, double-blind, randomized method, involved 24 healthy individuals over the age of 50 for 14 weeks. All those taking part were regular smokers of more than 10 cigarettes per day. During the first four weeks, one group was given a daily dose of 150 mg of Leucoselect Phytosome and the other group was given 150 mg of a placebo. After a three-week wash-out period, the second four-week stage followed during which the groups received the opposite treatment. At the end of each phase, the researchers found that treatment with Leucoselect Phytosome, compared with the placebo, induced a 20% reduction of the lipidic peroxidation, with a 15% increase of LDL resistance to oxidating stress. Leucoselect Phytosome is a complex containing a standardized extract based on procyanidins obtained from grape seeds and phospholipids from soy beans.
Omega 3's. Marine omega 3 EPA and DHA have been shown in several studies to play a crucial role in cardiovascular health. In 2002, The American Heart Association (AHA) stated, "Omega 3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of cardiovascular disease." Among the possible mechanisms of action, AHA noted that omega 3's reduce the susceptibility of the heart to arrhythmia, prevent the development of atherosclerosis and clot formation and slightly reduce blood pressure.
According to Baldur Hjaltason, area sales director, U.S., Pronova Biocare AS, Lysaker, Norway, one of the milestone studies was the GISSI-Prevenzione trial in Italy, which showed supplementation with a pharmaceutical grade of omega 3 EPA and DHA in more than 11,000 patients who survived a myocardial infarction significantly decreased sudden death by 45% and cardiovascular death by 30%.
The source of omega 3's is important, especially when comparing plant sources to marine sources. Mr. Hjaltason explained there has been ongoing debate as to whether the body can convert the medium chain omega 3 fatty acid, alpha linolenic acid (ALA) from flaxseed into EPA and DHA. Recent human studies indicate the conversion is poor and as such, ALA from flaxseed is not sufficient to cover the body's need for EPA and DHA," he said.
Mr. Hjaltason also commented on the application of EPA and DHA in functional foods. "This is an easy way to supply marine EPA and DHA into the diet," he said. "The marine oils are usually microencapsulated before being added to the functional food. However, technical challenges remain with regards to smell and taste." As a result he said foods with a short shelf-life are preferable for inclusion of marine omega 3's at the moment due to stability issues.
Policosanol. Based on current research, policosanol, which is derived from sugar cane, may be effective in lowering total cholesterol, LDL oxidation and the LDL-HDL ratio. According to Gilbert Gluck, president, Cyvex Nutrition, Irvine, CA, over a dozen double-blind, placebo-controlled clinical trials have been published to date, which document policosanol's efficacy, safety and tolerability in hyperlipdemic subjects. "The clinical studies have included short and long-term, placebo-controlled and comparative studies versus statins, fibrates, acipimox and probucol. In these published studies, policosanol intakes ranging from 2 to 20 mg/day have demonstrated statistically and clinically significant improvements in blood lipid parameters within the first eight to 12 weeks of use," he explained. "At a daily intake of 10 mg/day, total cholesterol decreased an average of 16% and LDL levels lowered 20-23% in three months. At 20 mg/day, LDL decreased by 30% after two months. At the same time, policosanol significantly increased HDL by an average of 21%. Canetti et. al. found that maximum effects were evident after 12 months of therapy and the treatment effect on total cholesterol and LDL was maintained during a two-year follow-up."
Niacin. Part of the vitamin B complex, niacin is a water-soluble vitamin required by the body for health, growth and reproduction. According to Lonza's Mr. Murray, four decades after the original research was conducted on niacin, it continues to be one of the most successful offerings for heart health. "Abnormal blood lipid (cholesterol) profiles remain one the most consistent risk factors of cardiovascular health. Niacin raises HDL and inhibits the synthesis of LDL and triglycerides," he said. "As one of the few ingredients that benefits the entire cholesterol profile, niacin was designated a 'first line therapy' by the National Institute's of Health (NIH) in 1988. Few heart health products have survived over 40 years of scrutiny and research as has niacin. Furthermore, sustained-release niacin products that reduce flushing have proven to be the most well accepted forms of niacin."
At the moment, Mr. Murrary said researchers are now combining niacin with other compounds to reduce harmful cholesterol and help raise good cholesterol. "This is exciting research because it may, for instance, allow doctors to reduce the dosage and side effects of statin drugs and still provide a significant cholesterol benefit," he said. "The future also looks bright for a combination of niacin and pantothene, a derivative of pantothenic acid, or vitamin B5."
L-carnitine. L-carnitine is an amino-acid-like substance that occurs naturally in the human body with high concentrations found in the heart. Explaining L-carnitine's function was Lonza's Paula Gaynor, associate director-Nutrition. "L-carnitine ensures the production of energy from fat," she said. "This role is critical for normal heart functioning as the heart itself gets most of the energy it needs from fat breakdown."
"Over the past few decades, the positive role of L-carnitine in heart health has been extensively documented in well-designed clinical research trials, thus establishing L-carnitine as one of the key dietary supplements for supporting heart health," Ms Gaynor said. "Not only is L-carnitine important for healthy heart functioning, clinical studies also indicate that this supplement has a role to play even after certain cardiovascular conditions, such as angina, heart failure and heart attack, have developed."
Vitamin K. Vitamin K is a newly recognized nutrient making its way into the heart health arena. It is found naturally in green leafy vegetables such as spinach and broccoli. There are two forms of vitamin K-K1 (phylloquinone) and K2 (menaquinone), however, it is K2 that has been receiving the attention for its heart health benefits. Eric Anderson, marketing director, Natural, Inc., Vernon Hills, IL, said that vitamin K has been traditionally used as a treatment to help blood coagulation. However, Mr. Anderson said that over the past two decades the discovery of a number of K-dependant proteins related to bone metabolism and vascular calcification has led to new interest in this vitamin.
Mr. Anderson explained vitamin K2's mechanism of action against arteriosclerosis. "One of the proteins involved in the regulation of calcium metabolism is GLA-protein. Recent research has established GLA-protein as a potent inhibitor of vascular calcification," he said. "However, this protein is active only after previous carboxylation by vitamin K. Inverse correlations between dietary intake and arterial calcification have been shown for both vitamin K1 and vitamin K2, however, the correlation was much stronger in the menaquinones, or K2."
Natto K2 is a newly available form of vitamin K from Natural, Inc. It is a branded proprietary extract of the traditional Japanese food natto, which is fermented from soybeans. According to Mr. Anderson, natto is the only known food that naturally contains vitamin K2 as menaquinone MK-7 in high amounts. "MK-7 is a form of K that is extremely bioavailable and proven to inhibit arterial calcification," he said.
Vitamin E. Vitamin E is an essential fat-soluble vitamin that includes eight naturally occurring compounds-four tocopherols and four tocotrienols. Each group of four is identified by the prefixes alpha, beta, gamma and delta and are available in both natural and synthetic forms.
Discussing vitamin E's role in the body was Ram Chaudhari, senior executive vice president, Research and Development, Fortitech, Schenectady, NY. "Vitamin E is an important antioxidant that helps maintain the integrity of cells. The main role of vitamin E in the body is to protect cell membranes and LDL from oxidation by free radicals," he said. "Because it is fat-soluble, vitamin E works particularly well in the lipophilic environment around the heart. It works at the cellular level all over the arteries and heart muscle." He added that vitamin E is most efficient in its natural d-alpha tocopherol form.
Recently, Zila Nutraceuticals, Prescott, AZ, launched its Ester-E ingredient, a unique vitamin E formed when natural d-alpha tocopherol is joined to a phosphate molecule during a patented process. According to the company, the resulting phosphate complex protects the antioxidant potential of vitamin E during absorption, transport and storage in the body.
The company also claims that while synthetic vitamin E in the form of dl-alpha tocopherol is the most common form of vitamin E available, studies have shown that natural vitamin E in the form of d-alpha tocopherol is better retained than synthetic versions. The company's research has also shown that the human body excretes synthetic vitamin E faster than the natural form.
Pycnogenol. Pycnogenol, from Natural Health Science, is the brand name of a natural plant extract originating from the bark of the Maritime pine, which grows along the coast of southwest France. According to Dr. Frank Schonlau, director of scientific communications, Pycnogenol contains a unique combination of procyanidins and bioflavonoids, which offer a wide range of health benefits. Recent research points to Pycnogenol's ability to reduce platelet activity, lower blood pressure, relax artery constriction and improve circulation.
Dr. Schonlau said that a central role of Pycnogenol is to act on a particular enzyme, endothelial nitric oxide synthase, in order to produce nitric oxide. "Nitric oxide counters the body's stress hormones, such as adrenaline," he said. "Stress hormones cause blood vessels to constrict. The body responds by telling the endothelial cells lining the blood vessels to produce more nitric oxide, allowing the body to return to a more relaxed state. Pycnogenol enhances this natural response by allowing the endothelial cells to produce a greater supply of nitric oxide to combat stress hormones."
According to studies, researchers recommend between 25 mg and 200 mg of Pycnogenol in order to combat cardiovascular risk factors and contribute to overall heart health and maintenance.
Oat Ingredients. FDA has recognized the importance of oat soluble fiber, specifically beta-glucan, which has been shown to effectively lower cholesterol. FDA has allowed it a health claim on food labels but in order to qualify for the heart health claim, a product must contain at least .75 grams of beta-glucan per serving. According to FDA, three grams of oat beta-glucan consumed daily provides a significant cholesterol-lowering benefit. However, this is often too much to consume through food, and as a result, a new generation of concentrated oat-based ingredients have hit the market.
OatVantage, from Nurture, Inc., is a highly concentrated oat soluble fiber containing up to 18 times the beta-glucan found in oats and is composed of 54% beta-glucan. "The proprietary technology behind OatVantage permits oat beta-glucan to be available in convenient, easy to consume capsules and foods," commented Mr. Stephens. "Beta-glucan lowers cholesterol by binding to cholesterol-rich bile acids in the intestine, preventing them from being reabsorbed into the bloodstream."
Mr. Stephens added that in addition to the cholesterol-lowering benefit of oat soluble fiber, research has also demonstrated a positive effect on several other cardiovascular risk factors, including attenuation of glycemic and insulinemic response. In addition, he said research has demonstrated positive effects of oat soluble fiber on hypertension and obesity.
Another offering on the oat ingredients front is Nutrim, which was originally developed by the United State Department of Agriculture (USDA). Today it is available from Van Drunen Farms as a low molecular weight beta-glucan ingredient possessing hypocholesterolemic and hypoglycemic properties. Offering his opinion on the heart healthy benefits of oat beta-glucan, Mr. Pond said it appears to promote an increase in the excretion of bile acids, which is thought to produce its cholesterol-lowering activity. Going into further detail, he said, "Oat beta-glucan may also promote cholesterol clearance from blood plasma via reverse-cholesterol transport. Additionally, it has been shown that as a healthy complex carbohydrate, oat beta glucan slows gastric emptying by increasing the viscosity of foods and slowing glucose uptake, leading to a more moderated insulin response."
Sytrinol. Sytrinol is a new patented proprietary formula derived from natural citrus and palm fruit extracts from SourceOne Global Partners, Chicago, IL. Unlike ingredients that attempt to block the absorption of cholesterol in the gastrointestinal tract, Sytrinol works to balance cholesterol production in the liver. Sytrinol combines citrus polymethoxylated flavones (PMFs), alpha, delta and gamma tocotrienols and other proprietary constituents. According to the company, this combination results in a synergistic effect for lowering total cholesterol, LDL cholesterol and triglyceride levels. Additionally, Sytrinol is a powerful antioxidant with numerous heart health benefits, including playing a role as an anti-inflammatory.
Earlier this year, SourceOne completed the first of three phases of a double-blinded, randomized 24-week study on 120 hypercholesterolemic subjects. The results from the completed 12-week Sytrinol clinical trial yielded positive results, which were consistent with previous clinical studies on Sytrinol's heart health benefits.
Arjuna. Arjuna (Teminalia arjuna), an Ayurvedic plant, has been shown to help coronary artery disease. Although many Ayurvedic plants have been shown to help coronary artery disease, according to Dr. Virender Sodhi, director, Ayurvedic and Naturopathic Clinic, Bellevue, WA, arjuna by far seems to be the best plant for heart health. This tree is commonly found close to a water source and it is the bark of the plant that is used for medicinal uses. "Arjuna extract has been shown to be a powerful antioxidant protecting the heart from oxidation. The anti-coagulant and anti-platelet aggregation action keeps the blood thin and lowers LDL, while increasing HDL," he said. "It also has cardioprotective, hypotensive and anti-inflammatory properties. In many animal model studies, arjuna extract has shown to reverse the damage to heart muscle. Its blood thinning abilities were comparable to those of aspirin and heparin, and it has also been used for bleeding disorders, which means it has adaptogenic actions."
Going into further detail, Dr. Sodhi said arjuna has been shown to be beneficial in patients with coronary heart disease in a number of studies. In one study when patients were given arjuna extract, the results were comparable to nitroglycerine in reversing angina and increasing exercise capacity, he said. "The numbers of angina attacks were reduced and 80% of patients received symptomatic relief." In animal studies arjuna has been shown to reverse plaque formation in the arteries and lower blood pressure. Dr. Sodhi said a typical dose of arjuna is 500 mg of standardized extract.
Guggul. Guggul is another form of treatment used in Ayurvedic medicine to help lower cholesterol, triglycerides and clean the arteries. According Ayush Herbs' Dr. Sodhi, numerous studies conducted both on humans and animals have shown gum guggul in a crude form, alcohol extract, petroleum ether extract and ethyl acetate extract to have an effective lipid-lowering effect, and all forms have shown to lower both elevated cholesterol and triglycerides. "Guggul's effects on cholesterol are highly favorable. It lowered VLDL and LDL cholesterol and at the same time increased HDL," commented Dr. Sodhi. "In various studies, it has also been shown to lower Lp(a) by 5-7% and C-reactive proteins (CRP) by 29%. Elevated levels of Lp(a) have been related to an increase in heart attacks and there are no known medications available to lower the Lp(a). CRP on the other hand, is quite a new concept, where inflammation is responsible for creating heart attacks."
In addition, Dr. Sodhi said gum guggul extract has been shown to prevent atherosclerosis and help in regression of arteriosclerotic plaques in animals. "Gum guggul extract has also shown to prevent the heart from free radical damage and improve overall heart metabolism."
Because the individual plays such an important role in heart health, with so much to gain, this category should continue to show major growth. "As we continue to identify more risk factors, the demographics for the heart health category will continue to grow. Improving cardiovascular health may well be one of greatest healthcare success stories of our time. Fortunately, long-term studies like the Framingham Heart Study, which is tracking generations of subjects, have provided a wealth of information," according to Lonza's Mr. Murray. "It wasn't too many years ago when the first symptom of heart disease was a full blown heart attack. The biggest challenge in moving forward and marketing heart health ingredients is cutting through the noise and distinguishing between products that are backed by well-designed human clinical trials demonstrating effectiveness and those that are supported by a few animal trials and a good story. This industry must point out ingredients and manufacturers that offer misleading products with no long-term solutions."
Natural Health Science's Mr. Assumma echoed these sentiments. "There are so many products out there and cutting through it all is the biggest issue the heart health category faces moving forward. There are so many people out there spending money, making noise and the reality is that there are only a handful of products on the market that are really beneficial," he said. "The obstacle that we are faced with is coming to the consumer with quality information that helps inform him or her about decisions that are appropriate for them to make when they are thinking about their health and making them understand that these products are not silver bullets. Another trend we will see emerge are more combination products for heart health."
In the end, Natural, Inc.'s Mr. Anderson said there needs to be a balance between the Western pharmaceutical model used to treat disease and natural alternatives that follow more of a preventative approach. "It's very possible if one knows that they're at risk for hypertension or other types of cardiovascular disease to exercise and make dietary choices that can help prevent that eventuality," he said. "As physicians become more aware of natural products that can help promote cardiovascular health, I hope that they'll begin to incorporate them into their treatment protocols."NW
Add to this the fact that consumers are becoming savvier about the negative side effects associated with pharmaceutical treatments, leading them to take preventative measures and seek natural alternatives, and it's hardly surprising then to find that the heart health category is one of the most dynamic areas of activity for both functional foods and dietary supplements.
Heart health is no longer just a "buzz word," according to Dan Murray, associate director-Nutrition, Lonza, Inc., Fair Lawn, NJ. "Most people now realize they are empowered to improve their heart health, extend their longevity and not simply perceive themselves as victims of their genetic make-up. This is a major development not only for the individual, but also for the healthcare system at large," he said. "Healthcare experts often talk about shifting the system from treatment to prevention, but few health concerns have the perceived payoff of cardiovascular care. Saving the system money may be a nice side effect, but living longer and living well is driving the individual effort on a daily basis."
Cardiovascular disease is not the consequence of a single isolated risk factor, but rather the end point of a complex process that starts early in life, according to Tova Arditi, scientific advisor, Solbar Plant Extracts, Ashdod, Israel. These include behavioral, environmental, socio-economic and genetic factors. "In order to prevent cardiovascular disease, it is necessary to simultaneously control the various risk factors and their determinants," he said. "Among the major risk factors are elevated blood lipids (cholesterol), diabetes, obesity and hypertension."
As heart disease is in part directly linked to diet, there are enormous opportunities for the natural products industry to formulate new heart healthy foods, beverages and supplements. Hartley Pond, technical sales manager, Van Drunen Farms, Santa Rosa, CA, offered his opinion on this opportunity. "Where the pharmaceutical industry tends to focus on people who are already sick with heart disease, the natural products and food industry has a great opportunity to develop foods and supplements that truly offer a strong level of prevention before we get sick," he said.
Heart Health Trends
As the heart health category continues accelerating its growth, it is becoming more vast and multifaceted. Neil Sullivan, director of sales, Kyowa Hakko USA, New York, NY, said he believes the heart health category will be a good complement to the standard large volume vitamin, mineral and bone health markets. "The category is many-sided because there are multiple ways to address heart health," he said. "There are supplements available that have a direct impact on heart health. Likewise, there are supplements that support active lifestyles and weight loss, which indirectly support long-term heart health goals."
During the last few years there has been a proliferation of ingredients that have come out slated for cardiovascular health. Commenting on this trend was Scott Larkin, director of marketing, LycoRed-Biodar USA, New York, NY. "Cardiovascular health affects everybody. As a result, from a marking perspective, it is a big category with a lot of potential," he said. "Unlike a few years ago, consumers have grasped the concept of cardiovascular health. They're looking for answers, which makes it a good time to market into the category because the education is better. The companies we sell to look for new ingredients to get an edge. As a result, there have been a lot of new formulas introduced in both supplements, functional foods and beverages."
In terms of identifying indicators regarding heart health, Frank Assumma, director of marketing, Natural Health Science, Hillside, NJ, has noticed in the last two years that people have begun to look at the issue of heart health a little differently. "People are not looking at individual markers so simply anymore, such as high cholesterol levels, for example. What we've found in the last couple of years is that there are other factors that might be even better indicators and one of them is inflammation," he said. "There is more medical evidence on the role of inflammation in heart disease and more emphasis on inflammation related markers, such as C-reactive protein (CRP)."
Mr. Assumma continued, "We normally think of inflammation as something that happens around the joints, but it can happen within the bloodstream too. When platelets stick together and clog up arteries, the blood vessels become inflamed and as a result it makes the vessel narrower. The integrity of the vessels in the vascular system has become much more of an issue as it relates to heart health."
Much of the growth in the heart health category is being driven by the aging of the population and an increased incidence of obesity, both which are related to increased cardiovascular disease, according to Greg Stephens, vice president, sales and marketing, Nuture, Inc., Devon, PA. "Unfortunately from a public health perspective, the cardiovascular health market continues to grow as the U.S. population ages and becomes more obese. Outcomes from research have placed more emphasis on controlling insulinemic response for maintaining healthy cardiovascular function. Lower serum insulin levels lead to lower LDL levels. In addition, to control insulin levels one must also maintain lower levels of serum glucose, or blood sugar," he explained. "There also seems to be more of an emphasis on providing comprehensive management of cardiovascular disease through the management of controllable, related cardiovascular risk factors, including elevated cholesterol, elevated blood sugar, hypertension, obesity and smoking."
The Functional Foods Front
Heart healthy functional foods like bars, cereals, smoothies and shakes, breads and pastas have been flourishing over the past several years. The growth in the market for these types offunctional foods is proof that consumers are showing an increased interest in proactively managing their heart health in variety of ways. As a result, consumer packaged goods companies are looking for ways to improve the health profile of their foods and beverages, and heart healthy products are high on the list. According to Pam Stauffer, marketing manager, Cargill, Inc., Minneapolis, MN. "Evidence of this in the market include recent product launches, such as Minute Maid Premium Heart Wise orange juice, Rice Dream Heartwise rice milk and Lifetime lowfat cheeses.
Three major strategies are used in the marketing of functional foods for heart health, according Solbar's Mr. Arditi. "One strategy focuses on identifying the intrinsic benefits of existing components of the diet and leveraging these through nutrition marketing," he offered. "A quite different strategy focuses on identifying specific ingredients with heart health or cholesterol-lowering potential and adding these ingredients into a wide variety of foods-almost always foods in which the ingredients would not naturally be found in any significant quantities. And it is this strategy that has been the greatest focus of attention thus far for industry scientists, marketers and investors." Mr. Arditi said the third strategy is to exchange ingredients in foods that have been identified with an elevated risk for heart disease, for example, substituting the hydrogenated oils used in margarines and bakery products with plant stanols.
While the functional food segment seems like a good avenue of opportunity, something must be done from a regulatory perspective to facilitate innovation. Kyowa Hakko's Mr. Sullivan said it is the government's responsibility to raise the incentive for food companies to invest more within this category. "To motivate a majority of food companies to invest their money in the functional food category, a more relaxed regulation that gives the final product containing a proprietary ingredient a health claim could be one solution-similar to the Foods for Specified Health Uses (FOSHU) system in Japan," he said. "This system will enable the food companies to work on developing novel active compounds. The current framework allows only a limited number of commodity-type compounds to take advantage of the health claim regulation, and companies have to stick to those types of compounds if they want to use a health claim. This will limit both the category and the number of final products. What is worse, it will not motivate companies to discover new ingredients, which is a key driver necessary for the expansion of the functional food market."
Consumer Awareness
A major factor propelling the heart health category forward is the increased level of consumer awareness. Part of the equation relates to consumers becoming much more knowledgeable about the negative side effects associated with the statin drugs, said Nurture's Mr. Stephens. "Even if nutritional interventions do not allow people to eliminate the use of statins, lowering the dose would impart a positive benefit. Over the past few years consumers have become more educated, focusing on lowering LDL," he said. "Connected to this is new research demonstrating that lowering LDL as much as possible has positive outcomes. For those with high cholesterol (>240mg/dL), consumers and medical professionals alike are looking to combine lifestyle modifications, including dietary changes, with pharmaceutical interventions, such as statin drugs."
Because the cardiovascular health category is so broad, it has the capability of supporting several products. The problem with that, Mr. Murray said, is consumer education has been so good that consumers have difficulty deciding which products to try and which ones to forego. "Daily supplement packs have done a nice job of meeting consumer needs both in delivering a variety of products and making the products convenient to use," he said. "However, most people still trust their healthcare provider to deliver information and treatments. Although today, they are more willing to ask questions of their healthcare provider rather than accept a standard treatment without explanation."
Natural Health Science's Mr. Assumma said the mass proliferation of products is not good for consumers because it creates confusion. "I think, like in most categories, there is just way too much information out there for consumers," he said. "Consumers who are knowledgeable and interested can pick up several journals or go online and get a lot of information, but there is almost too much information. Part of the problem in the category is that when you go to a pharmacy, drug store or just a regular health food store, it is very difficult to sort through the aisles and differentiate between products."
Cardiovascular Ingredients
Lycopene. The image of the tomato is becoming synonymous with heart health, mostly because of large consumer ad campaigns, including that from Centrum. Lycopene is the main active constituent in tomatoes, which has been a recent focus in cardiovascular research. According to LycoRed's Mr. Larkin, lycopene has been shown to reduce hypertension and LDL cholesterol oxidation, both of which lead to plaque build-up in the arteries. LycoRed supplies Lyc-O-Mato, an all-natural extract of tomatoes standardized to contain 6% lycopene, in addition to a variety of other phytonutrients, including beta-carotene, tocopherols, phytosterols, phytoene and phytofluene.
When studied in relation to hypertension, a 250 mg daily dose of Lyc-O-Mato, which contains 15 mg of lycopene, was shown to reduce systolic blood pressure significantly. Another study found that Lyc-O-Mato protects LDL cholesterol from oxidative modification. In the study, Lyc-O-Mato made LDL cholesterol 90% more resistant to oxidation.
Mr. Larkin said that because of the clinical studies validating lycopene's effectiveness in supporting cardiovascular health, it is a hot ingredient that is in demand. However, he also said that while mainstream consumers are making the connection between tomatoes and heart health, they are not educated enough to know the difference between the natural and synthetic forms and are being misled. "The clinical studies in which lycopene was shown to reduce hypertension and LDL cholesterol were based on 15 mg of natural lycopene taken twice a day. There is only 300 mcg of synthetic lycopene in Centrum, which is not enough to experience heart health benefits," he said. "They're putting a synthetic splash in there just for label claim because lycopene is a hot ingredient. What we see coming from USP in the near future is that they're going to make companies identify on the label whether or not the lycopene contained within is a natural tomato extract or if it is synthetic lycopene. The challenge we face is getting consumers educated enough to look for natural tomato lycopene."
Soy Protein. Soy contains several different nutrients, however, the two that get the most attention are soy protein and soy isoflavones. Most research has focused on soy protein and since FDA approved a health claim in 1999 stating, "25 grams of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease," soy protein's popularity has really taken off in the heart health category.
In addition to soy protein's cholesterol-lowering properties, which most people are aware of because of the heart health claim, Geri Berdak, manager of public affairs, The Solae Company, St. Louis, MO, said that there are other factors that soy protein impacts to help reduce the risk of heart disease. "Soy protein has been shown to alter the way the liver metabolizes cholesterol, reducing it from the bloodstream," she said. "There has also been research conducted showing it helps arteries retain their elasticity."
Soy isoflavones also display similar cholesterol-lowering qualities, in addition to other heart health benefits, according to Jocelyn Mathern, technical specialist, Acatris, Inc., Minneapolis, MN. However, Ms. Mathern said, research has highlighted the synergism between both soy protein and soy isoflavones, which when taken together impart the most benefits. "Going back a few years, researchers wanted to know which, with regard to lowering cholesterol, was more beneficial-soy protein or soy isoflavones." she said. "The researchers fed a soy protein isolate with all of its naturally occurring isoflavones to one group of people and then they fed a soy protein isolate with its isoflavones removed to another group. The group that had consumed the soy protein isolate with its naturally occurring isoflavones had lower cholesterol levels, but the group that was fed the soy protein isolate without its isoflavones experienced no effect."
Kyowa Hakko was recently granted generally recognized as safe status (GRAS) by FDA for its newly developed soy peptide, CSPHP, an abbreviation for C-fraction soy protein hydrolysate with bound phospholipids, which may also play a role in promoting healthy cholesterol levels. Explaining CSPHP's mechanism of action was Mr. Sullivan. "CSPHP blocks cholesterol absorption at the intestinal level. It has a completely different mechanism than that of statin drugs," he said. "CSPHP works by interfering in the micelle formation, which is essential for cholesterol to be absorbed via the intestinal wall, and also by binding to the bile acid and pushing it out of the body."
CSPHP can be provided in tablet form or used as an ingredient in a wide range of food products. In fact, beverage products in Japan with formulations that include CSPHP have already been approved by Japan's Ministry of Health, Labor and Welfare (MHLW) as FOSHU, according to the company.
Plant sterols. Plant sterols have been shown in studies to reduce LDL cholesterol by 8-15%. "They are structurally similar to cholesterol and they compete with the cholesterol humans ingest for absorption through the small intestine," explained Cargill's Ms. Stauffer. Cargill's branded line of plant sterols, CoroWise, which are derived from natural grains including soy, corn and sunflower, recently received a lot of attention due to its inclusion in Minute Maid Premium Heart Wise orange juice.
Discussing plant sterols' mechanism of action, Ms. Stauffer said that the more phytosterols present in the intestine following a meal, the less cholesterol absorption will occur. In addition, she said, "The plant sterols that are consumed are not absorbed to any appreciable extent. When plant sterols are consumed, they not only inhibit the uptake of cholesterol by the body, but they are flushed through the system as well."
Grape Seed. The polyphenols found in grape seeds have received a lot of attention for their cardiovascular health properties. Ron Martin, vice president of sales, Polyphenolics, Inc., Granger, IN, said that the company has been doing a lot work with both its grape seed extract and grape pomace extract in the area of endothelial cell function. "Endothelial cells have to function properly or else arteriosclerosis will progress," he said. "We've done work to show that our grape seed extract and grape pomace extract were both effective in preventing hypertension and lowering cholesterol." Mr. Martin added that the company is about one and half to two years away from going after a qualified health claim, which it needs to obtain in order to expand into the food and beverage industry.
Researches using Italy-based Indena's grape seed extract, Leucoselect Phytosome, found that the ingredient protects easily oxidized LDL cholesterol under oxidative stress as observed in heavy smokers. This clinical study, conducted against placebo using the crossover, double-blind, randomized method, involved 24 healthy individuals over the age of 50 for 14 weeks. All those taking part were regular smokers of more than 10 cigarettes per day. During the first four weeks, one group was given a daily dose of 150 mg of Leucoselect Phytosome and the other group was given 150 mg of a placebo. After a three-week wash-out period, the second four-week stage followed during which the groups received the opposite treatment. At the end of each phase, the researchers found that treatment with Leucoselect Phytosome, compared with the placebo, induced a 20% reduction of the lipidic peroxidation, with a 15% increase of LDL resistance to oxidating stress. Leucoselect Phytosome is a complex containing a standardized extract based on procyanidins obtained from grape seeds and phospholipids from soy beans.
Omega 3's. Marine omega 3 EPA and DHA have been shown in several studies to play a crucial role in cardiovascular health. In 2002, The American Heart Association (AHA) stated, "Omega 3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of cardiovascular disease." Among the possible mechanisms of action, AHA noted that omega 3's reduce the susceptibility of the heart to arrhythmia, prevent the development of atherosclerosis and clot formation and slightly reduce blood pressure.
According to Baldur Hjaltason, area sales director, U.S., Pronova Biocare AS, Lysaker, Norway, one of the milestone studies was the GISSI-Prevenzione trial in Italy, which showed supplementation with a pharmaceutical grade of omega 3 EPA and DHA in more than 11,000 patients who survived a myocardial infarction significantly decreased sudden death by 45% and cardiovascular death by 30%.
The source of omega 3's is important, especially when comparing plant sources to marine sources. Mr. Hjaltason explained there has been ongoing debate as to whether the body can convert the medium chain omega 3 fatty acid, alpha linolenic acid (ALA) from flaxseed into EPA and DHA. Recent human studies indicate the conversion is poor and as such, ALA from flaxseed is not sufficient to cover the body's need for EPA and DHA," he said.
Mr. Hjaltason also commented on the application of EPA and DHA in functional foods. "This is an easy way to supply marine EPA and DHA into the diet," he said. "The marine oils are usually microencapsulated before being added to the functional food. However, technical challenges remain with regards to smell and taste." As a result he said foods with a short shelf-life are preferable for inclusion of marine omega 3's at the moment due to stability issues.
Policosanol. Based on current research, policosanol, which is derived from sugar cane, may be effective in lowering total cholesterol, LDL oxidation and the LDL-HDL ratio. According to Gilbert Gluck, president, Cyvex Nutrition, Irvine, CA, over a dozen double-blind, placebo-controlled clinical trials have been published to date, which document policosanol's efficacy, safety and tolerability in hyperlipdemic subjects. "The clinical studies have included short and long-term, placebo-controlled and comparative studies versus statins, fibrates, acipimox and probucol. In these published studies, policosanol intakes ranging from 2 to 20 mg/day have demonstrated statistically and clinically significant improvements in blood lipid parameters within the first eight to 12 weeks of use," he explained. "At a daily intake of 10 mg/day, total cholesterol decreased an average of 16% and LDL levels lowered 20-23% in three months. At 20 mg/day, LDL decreased by 30% after two months. At the same time, policosanol significantly increased HDL by an average of 21%. Canetti et. al. found that maximum effects were evident after 12 months of therapy and the treatment effect on total cholesterol and LDL was maintained during a two-year follow-up."
Niacin. Part of the vitamin B complex, niacin is a water-soluble vitamin required by the body for health, growth and reproduction. According to Lonza's Mr. Murray, four decades after the original research was conducted on niacin, it continues to be one of the most successful offerings for heart health. "Abnormal blood lipid (cholesterol) profiles remain one the most consistent risk factors of cardiovascular health. Niacin raises HDL and inhibits the synthesis of LDL and triglycerides," he said. "As one of the few ingredients that benefits the entire cholesterol profile, niacin was designated a 'first line therapy' by the National Institute's of Health (NIH) in 1988. Few heart health products have survived over 40 years of scrutiny and research as has niacin. Furthermore, sustained-release niacin products that reduce flushing have proven to be the most well accepted forms of niacin."
At the moment, Mr. Murrary said researchers are now combining niacin with other compounds to reduce harmful cholesterol and help raise good cholesterol. "This is exciting research because it may, for instance, allow doctors to reduce the dosage and side effects of statin drugs and still provide a significant cholesterol benefit," he said. "The future also looks bright for a combination of niacin and pantothene, a derivative of pantothenic acid, or vitamin B5."
L-carnitine. L-carnitine is an amino-acid-like substance that occurs naturally in the human body with high concentrations found in the heart. Explaining L-carnitine's function was Lonza's Paula Gaynor, associate director-Nutrition. "L-carnitine ensures the production of energy from fat," she said. "This role is critical for normal heart functioning as the heart itself gets most of the energy it needs from fat breakdown."
"Over the past few decades, the positive role of L-carnitine in heart health has been extensively documented in well-designed clinical research trials, thus establishing L-carnitine as one of the key dietary supplements for supporting heart health," Ms Gaynor said. "Not only is L-carnitine important for healthy heart functioning, clinical studies also indicate that this supplement has a role to play even after certain cardiovascular conditions, such as angina, heart failure and heart attack, have developed."
Vitamin K. Vitamin K is a newly recognized nutrient making its way into the heart health arena. It is found naturally in green leafy vegetables such as spinach and broccoli. There are two forms of vitamin K-K1 (phylloquinone) and K2 (menaquinone), however, it is K2 that has been receiving the attention for its heart health benefits. Eric Anderson, marketing director, Natural, Inc., Vernon Hills, IL, said that vitamin K has been traditionally used as a treatment to help blood coagulation. However, Mr. Anderson said that over the past two decades the discovery of a number of K-dependant proteins related to bone metabolism and vascular calcification has led to new interest in this vitamin.
Mr. Anderson explained vitamin K2's mechanism of action against arteriosclerosis. "One of the proteins involved in the regulation of calcium metabolism is GLA-protein. Recent research has established GLA-protein as a potent inhibitor of vascular calcification," he said. "However, this protein is active only after previous carboxylation by vitamin K. Inverse correlations between dietary intake and arterial calcification have been shown for both vitamin K1 and vitamin K2, however, the correlation was much stronger in the menaquinones, or K2."
Natto K2 is a newly available form of vitamin K from Natural, Inc. It is a branded proprietary extract of the traditional Japanese food natto, which is fermented from soybeans. According to Mr. Anderson, natto is the only known food that naturally contains vitamin K2 as menaquinone MK-7 in high amounts. "MK-7 is a form of K that is extremely bioavailable and proven to inhibit arterial calcification," he said.
Vitamin E. Vitamin E is an essential fat-soluble vitamin that includes eight naturally occurring compounds-four tocopherols and four tocotrienols. Each group of four is identified by the prefixes alpha, beta, gamma and delta and are available in both natural and synthetic forms.
Discussing vitamin E's role in the body was Ram Chaudhari, senior executive vice president, Research and Development, Fortitech, Schenectady, NY. "Vitamin E is an important antioxidant that helps maintain the integrity of cells. The main role of vitamin E in the body is to protect cell membranes and LDL from oxidation by free radicals," he said. "Because it is fat-soluble, vitamin E works particularly well in the lipophilic environment around the heart. It works at the cellular level all over the arteries and heart muscle." He added that vitamin E is most efficient in its natural d-alpha tocopherol form.
Recently, Zila Nutraceuticals, Prescott, AZ, launched its Ester-E ingredient, a unique vitamin E formed when natural d-alpha tocopherol is joined to a phosphate molecule during a patented process. According to the company, the resulting phosphate complex protects the antioxidant potential of vitamin E during absorption, transport and storage in the body.
The company also claims that while synthetic vitamin E in the form of dl-alpha tocopherol is the most common form of vitamin E available, studies have shown that natural vitamin E in the form of d-alpha tocopherol is better retained than synthetic versions. The company's research has also shown that the human body excretes synthetic vitamin E faster than the natural form.
Pycnogenol. Pycnogenol, from Natural Health Science, is the brand name of a natural plant extract originating from the bark of the Maritime pine, which grows along the coast of southwest France. According to Dr. Frank Schonlau, director of scientific communications, Pycnogenol contains a unique combination of procyanidins and bioflavonoids, which offer a wide range of health benefits. Recent research points to Pycnogenol's ability to reduce platelet activity, lower blood pressure, relax artery constriction and improve circulation.
Dr. Schonlau said that a central role of Pycnogenol is to act on a particular enzyme, endothelial nitric oxide synthase, in order to produce nitric oxide. "Nitric oxide counters the body's stress hormones, such as adrenaline," he said. "Stress hormones cause blood vessels to constrict. The body responds by telling the endothelial cells lining the blood vessels to produce more nitric oxide, allowing the body to return to a more relaxed state. Pycnogenol enhances this natural response by allowing the endothelial cells to produce a greater supply of nitric oxide to combat stress hormones."
According to studies, researchers recommend between 25 mg and 200 mg of Pycnogenol in order to combat cardiovascular risk factors and contribute to overall heart health and maintenance.
Oat Ingredients. FDA has recognized the importance of oat soluble fiber, specifically beta-glucan, which has been shown to effectively lower cholesterol. FDA has allowed it a health claim on food labels but in order to qualify for the heart health claim, a product must contain at least .75 grams of beta-glucan per serving. According to FDA, three grams of oat beta-glucan consumed daily provides a significant cholesterol-lowering benefit. However, this is often too much to consume through food, and as a result, a new generation of concentrated oat-based ingredients have hit the market.
OatVantage, from Nurture, Inc., is a highly concentrated oat soluble fiber containing up to 18 times the beta-glucan found in oats and is composed of 54% beta-glucan. "The proprietary technology behind OatVantage permits oat beta-glucan to be available in convenient, easy to consume capsules and foods," commented Mr. Stephens. "Beta-glucan lowers cholesterol by binding to cholesterol-rich bile acids in the intestine, preventing them from being reabsorbed into the bloodstream."
Mr. Stephens added that in addition to the cholesterol-lowering benefit of oat soluble fiber, research has also demonstrated a positive effect on several other cardiovascular risk factors, including attenuation of glycemic and insulinemic response. In addition, he said research has demonstrated positive effects of oat soluble fiber on hypertension and obesity.
Another offering on the oat ingredients front is Nutrim, which was originally developed by the United State Department of Agriculture (USDA). Today it is available from Van Drunen Farms as a low molecular weight beta-glucan ingredient possessing hypocholesterolemic and hypoglycemic properties. Offering his opinion on the heart healthy benefits of oat beta-glucan, Mr. Pond said it appears to promote an increase in the excretion of bile acids, which is thought to produce its cholesterol-lowering activity. Going into further detail, he said, "Oat beta-glucan may also promote cholesterol clearance from blood plasma via reverse-cholesterol transport. Additionally, it has been shown that as a healthy complex carbohydrate, oat beta glucan slows gastric emptying by increasing the viscosity of foods and slowing glucose uptake, leading to a more moderated insulin response."
Sytrinol. Sytrinol is a new patented proprietary formula derived from natural citrus and palm fruit extracts from SourceOne Global Partners, Chicago, IL. Unlike ingredients that attempt to block the absorption of cholesterol in the gastrointestinal tract, Sytrinol works to balance cholesterol production in the liver. Sytrinol combines citrus polymethoxylated flavones (PMFs), alpha, delta and gamma tocotrienols and other proprietary constituents. According to the company, this combination results in a synergistic effect for lowering total cholesterol, LDL cholesterol and triglyceride levels. Additionally, Sytrinol is a powerful antioxidant with numerous heart health benefits, including playing a role as an anti-inflammatory.
Earlier this year, SourceOne completed the first of three phases of a double-blinded, randomized 24-week study on 120 hypercholesterolemic subjects. The results from the completed 12-week Sytrinol clinical trial yielded positive results, which were consistent with previous clinical studies on Sytrinol's heart health benefits.
Arjuna. Arjuna (Teminalia arjuna), an Ayurvedic plant, has been shown to help coronary artery disease. Although many Ayurvedic plants have been shown to help coronary artery disease, according to Dr. Virender Sodhi, director, Ayurvedic and Naturopathic Clinic, Bellevue, WA, arjuna by far seems to be the best plant for heart health. This tree is commonly found close to a water source and it is the bark of the plant that is used for medicinal uses. "Arjuna extract has been shown to be a powerful antioxidant protecting the heart from oxidation. The anti-coagulant and anti-platelet aggregation action keeps the blood thin and lowers LDL, while increasing HDL," he said. "It also has cardioprotective, hypotensive and anti-inflammatory properties. In many animal model studies, arjuna extract has shown to reverse the damage to heart muscle. Its blood thinning abilities were comparable to those of aspirin and heparin, and it has also been used for bleeding disorders, which means it has adaptogenic actions."
Going into further detail, Dr. Sodhi said arjuna has been shown to be beneficial in patients with coronary heart disease in a number of studies. In one study when patients were given arjuna extract, the results were comparable to nitroglycerine in reversing angina and increasing exercise capacity, he said. "The numbers of angina attacks were reduced and 80% of patients received symptomatic relief." In animal studies arjuna has been shown to reverse plaque formation in the arteries and lower blood pressure. Dr. Sodhi said a typical dose of arjuna is 500 mg of standardized extract.
Guggul. Guggul is another form of treatment used in Ayurvedic medicine to help lower cholesterol, triglycerides and clean the arteries. According Ayush Herbs' Dr. Sodhi, numerous studies conducted both on humans and animals have shown gum guggul in a crude form, alcohol extract, petroleum ether extract and ethyl acetate extract to have an effective lipid-lowering effect, and all forms have shown to lower both elevated cholesterol and triglycerides. "Guggul's effects on cholesterol are highly favorable. It lowered VLDL and LDL cholesterol and at the same time increased HDL," commented Dr. Sodhi. "In various studies, it has also been shown to lower Lp(a) by 5-7% and C-reactive proteins (CRP) by 29%. Elevated levels of Lp(a) have been related to an increase in heart attacks and there are no known medications available to lower the Lp(a). CRP on the other hand, is quite a new concept, where inflammation is responsible for creating heart attacks."
In addition, Dr. Sodhi said gum guggul extract has been shown to prevent atherosclerosis and help in regression of arteriosclerotic plaques in animals. "Gum guggul extract has also shown to prevent the heart from free radical damage and improve overall heart metabolism."
Looking Ahead
Because the individual plays such an important role in heart health, with so much to gain, this category should continue to show major growth. "As we continue to identify more risk factors, the demographics for the heart health category will continue to grow. Improving cardiovascular health may well be one of greatest healthcare success stories of our time. Fortunately, long-term studies like the Framingham Heart Study, which is tracking generations of subjects, have provided a wealth of information," according to Lonza's Mr. Murray. "It wasn't too many years ago when the first symptom of heart disease was a full blown heart attack. The biggest challenge in moving forward and marketing heart health ingredients is cutting through the noise and distinguishing between products that are backed by well-designed human clinical trials demonstrating effectiveness and those that are supported by a few animal trials and a good story. This industry must point out ingredients and manufacturers that offer misleading products with no long-term solutions."
Natural Health Science's Mr. Assumma echoed these sentiments. "There are so many products out there and cutting through it all is the biggest issue the heart health category faces moving forward. There are so many people out there spending money, making noise and the reality is that there are only a handful of products on the market that are really beneficial," he said. "The obstacle that we are faced with is coming to the consumer with quality information that helps inform him or her about decisions that are appropriate for them to make when they are thinking about their health and making them understand that these products are not silver bullets. Another trend we will see emerge are more combination products for heart health."
In the end, Natural, Inc.'s Mr. Anderson said there needs to be a balance between the Western pharmaceutical model used to treat disease and natural alternatives that follow more of a preventative approach. "It's very possible if one knows that they're at risk for hypertension or other types of cardiovascular disease to exercise and make dietary choices that can help prevent that eventuality," he said. "As physicians become more aware of natural products that can help promote cardiovascular health, I hope that they'll begin to incorporate them into their treatment protocols."NW