Cardiovascular disease is a huge obstacle facing the U.S., with far-reaching consequences impacting the nation’s population, economy and healthcare system.

Data from the American Heart Association (AHA) indicated that approximately 83.6 million Americans, or one in three adults, suffer from some form of cardiovascular disease (CVD), including conditions such as high blood pressure, coronary heart disease, heart failure, stroke and congenital cardiovascular defects. 

AHA research (Circulation, 2011) also predicted that between 2010 and 2030, medical costs related to CVD could nearly triple, growing from $273 billion to $818 billion. Indirect costs of CVD due to loss of productivity also add to this burden. From 2010-2030 it is anticipated that these indirect expenses will grow by 61%, from $172 billion in 2010 to $276 billion in 2030. The report concluded that estimates for real and indirect medical costs related to CVD could reach well over $1 trillion by 2030.

In response to this growing epidemic, nutraceutical products for heart health have emerged as preventive tools in the fight against CVD. In fact, the 2014 Consumer Survey on Dietary Supplements from the Council for Responsible Nutrition (CRN), Washington, D.C., found that 22% of supplement users take supplements specifically targeting heart health.

“Consumer heart health products have exploded in popularity the last few years,” commented Steve Siegel, vice president of Ecuadorian Rainforest, LLC, Belleville, NJ. “It is a hot market right now and it’s no surprise. Consumers are looking for products to not only keep their hearts healthy but also to help fortify it. Many are choosing natural ingredients because they are looking for an alternative to pharmaceutical products.”

To meet this demand a variety of foods, beverages and supplements have emerged to support consumers seeking “heart healthy” product offerings. Euromonitor International reported that dietary supplements positioned for heart health accounted for 12.3% of all supplement launches in 2014.

Eric Anderson, senior vice president, global sales & marketing with NattoPharma USA, Inc. (Metuchen, NJ), the North American subsidiary of NattoPharma ASA (Hovik, Norway), believes cardiovascular health is a top concern for consumers, and suggested that many are looking to protect their heart earlier in life, before a serious health issue ensues. “In turn, cardiovascular support products are a top category in the natural channel and beyond,” he said.

Broad Appeal
With the vast number and diverse range of people impacted by CVD, different nutraceutical solutions have been developed to meet the needs of specific consumer groups.

The traditional audience for such products is an aging population, according to Dean Mosca, president of Proprietary Nutritionals Inc., Kearny, NJ. “The clear target populations for cardiovascular support supplements remain middle-aged and the young elderly,” he said. “Notwithstanding congenital issues, cardiovascular status is largely determined by years of lifestyle—diet, exercise (or lack thereof), body composition and smoking/excessive alcohol consumption. Lifestyle factors take years to impact cardiovascular function, from the layering of arterial plaque to unhealthy cholesterol profiles.”

Annie Eng, CEO, HP Ingredients, Bradenton, FL, suggested the target audience for heart health supplements is in their 30s or 40s, and are active consumers through their 70s. However, she has observed younger demographics becoming consumers in the marketplace as well. “In the U.S. there is an increase in the number of children who are obese and overweight, often leading to early onset of metabolic syndrome, which encompasses cardiovascular issues if the condition is allowed to continue unabated.” She predicted opportunities in the market for children’s supplements formulated for heart health.

Sébastien Bornet, vice president of global sales and marketing at Switzerland-based Horphag Research (the exclusive worldwide supplier of Pycnogenol French maritime pine bark extract) believes massive need among a diverse audience will keep the supplement category strong. He commented, “Heart health is an application that is important for both men and women throughout their life. As the leading causes of death and disability in the United States, heart diseases and other cardiovascular health issues are the number one concerns for Americans.”

Essential Ingredients
Numerous clinically validated ingredients supporting heart health are making strides in the marketplace.

Among the more popular is Coenzyme Q10 (CoQ10), an ingredient which the CoQ10 Association, Salt Lake City, UT, estimates 12 million Americans use daily. CoQ10 provides support for producing energy throughout the body, demonstrating particular benefits for the heart muscle tissue. In addition, supplementation with CoQ10 has been found to support cardiovascular health in athletes, people under extreme stress, and to fill general nutritional gaps as a result of a poor diet.

CoQ10 deficiency is also linked to statin use, a commonly prescribed drug used to manage high blood pressure. It is estimated that 40.8 million adults age 18 or older took prescription statins between 2010 and 2011 (Agency for Healthcare Research and Quality, 2014).

To explore CoQ10 usage among this large population the CoQ10 Association commissioned a study with Research Now surveying 100 cardiologists to determine their prescribing habits of statins and their views on supplements. “The survey indicated 100% of the cardiologists questioned prescribed a statin drug to their patients for heart health purposes. The effect of statin therapy on CoQ10 levels has been well demonstrated, but the benefits of CoQ10 supplementation to statin patients has not,” commented Executive Director of the CoQ10 Association Scott Steinford.

He added that 71% of the cardiologists surveyed recommended CoQ10 to some segment of their patient population, but did so based primarily on anecdotal evidence or patient requests. “There have only been a few clinical studies conducted to investigate the impact of CoQ10 supplementation on statin patients with mixed results. It is hoped more studies can be appropriately constructed to provide more conclusive evidence of benefit.”

One such study demonstrating CoQ10’s benefits for statin users (Medical Science Monitor, 2014) found CoQ10 supplementation of 50 mg twice daily reduced statin-related mild-to-moderate muscular symptoms during daily activities.

Oxidation of cholesterol is a known factor in the development of heart disease, which is why antioxidant supplements targeting heart health have emerged as popular nutraceuticals in the category.

Harnessing the potential of antioxidants, Natreon’s Capros provides a vegetarian, organic, non-GMO and Generally Recognized As Safe (GRAS) cardiovascular product derived from the edible fruits of Phyllanthus emblica (amla). “Unlike CoQ10 and fish oils, Capros is completely water-soluble and stable, making it suitable for both solid dosage forms as well as hot and cold beverages,” explained Jeff Lind, vice president of sales & marketing for the New Brunswick, NJ-based company.

Capros is backed by eight human clinical studies in type 2 diabetics, healthy volunteers and in pre-metabolic syndrome subjects, he said. “These studies have shown significant improvements in endothelial function by increasing levels of nitric oxide up to 50% in the body. Capros significantly decreases the inflammation biomarker hsCRP [high-sensitivity C-reactive protein] by more than 50%,” noted Mr. Lind, adding that endothelial dysfunction and systemic inflammation are implicated in declining cardiovascular health. 

“In addition, Capros significantly improves the lipid profile by lowering LDL, triglycerides and total cholesterol and increasing HDL. A mechanism of action study was recently conducted at the University of Connecticut Medical Center which showed that Capros works on several different pathways to improve cardiovascular health, including the GSK3β-β Catenin pathway.” Capros was tolerated well in all studies without any major adverse effects reported, he added.

Vitamin E tocotrienols—derived from rice, palm and annatto—are another antioxidant tool to support cardiovascular health. Research published in the Journal of Clinical & Experimental Cardiology in April 2015 found vitamin E tocotrienols from annatto (125-750 mg/day, at an optimum dose of 250 mg/day) reduced inflammation and oxidative stress biomarkers associated with cardiovascular disease and aging after four weeks of supplementation.

An additional study published this year in the British Journal of Medicine & Medical Research concluded that annatto tocotrienol (mainly composed of delta-tocotrienol) improved cardiovascular risk factors such as cholesterol, triglycerides and inflammatory cytokines. In a four-week study using 125-750 mg/day (an optimum is 250 mg/day), along with healthy eating habits, annatto tocotrienol was found to reduce blood lipid levels significantly. Both studies used the DeltaGold annatto tocotrienol ingredient supplied by American River Nutrition, Hadley, MA, which typically contains ~90% delta- and 10% gamma-tocotrienol.

A botanical solution for maintaining a healthy heart, Bergamonte contains bioactive compounds extracted from the juice and albedo of Citrus bergamia risso. Standardized to > 30% polyphenolic flavonoids, these compounds include naringin, neohesperidin, neoeriocitrin, 1% melitidine and 2% brutelidine, explained HP Ingredient’s Ms. Eng. “These flavonoids are clinically proven to help maintain healthy cholesterol levels, healthy blood glucose level, and increase HDL cholesterol,” she added.

An unpublished human clinical trial involving 192 subjects evaluated supplementation of 100 ml of Bergamonte for 30 days. Results found reduction of total cholesterol by 35.72%, HDL improvement of 56.05%, LDL decrease by 41.95% and lowered triglycerides of 38.31%.

The leaves of olive trees have been used since ancient times as a means to combat high blood pressure, atherosclerosis and diabetes, as well as other health issues, according to Switzerland-based Frutarom BU Health. Utilizing this traditional remedy, the company developed Benolea olive leaf extract (Olea europaea L.) positioned for cardiovascular support. The potent antioxidant offers high oleuropein and polyphenol content, with a high degree of purity, thanks to the company’s patented EFLA HyperPure process.

Research suggests that Benolea lowered blood pressure dose-dependently in a trial examining adult twins, as well as supported a significant reduction in LDL cholesterol (Phytotherapy Research, 2008). Additional research demonstrated that Benolea effectively lowered blood pressure in subjects with stage-1 hypertension (Phytomedicine, 2011).

Pycnogenol, a French maritime pine bark extract, provides benefits to the cardiovascular system, including normalization of blood pressure and platelet function, improvement of blood lipids, as well as blood sugar values, noted Horphag’s Mr. Bornet. Adding to the company’s breadth of research supporting the ingredient’s efficacy, a new study published in the Journal of International Angiology found supplementation with the botanical extract might help improve endothelial function for those with borderline hypertension, hyperglycemia or hyperlipidemia.

In the trial 49 participants took Pycnogenol (50 mg/three times daily) in combination with a controlled health plan—including a reduction of carbohydrates and caffeinated drinks and daily exercise—while 43 participants in the control group followed the controlled health plan alone.

Subjects were evaluated at eight and 12 weeks. Daily supplementation with Pycnogenol was shown to significantly improve endothelial function by 55% after eight weeks of supplementation and 66% after 12 weeks of supplementation. Additionally, researchers found a significant reduction in oxidative stress by 20%, and normalization of blood pressure in subjects with borderline hypertension. Additional benefits included a reduction of cholesterol levels in participants with borderline hyperlipidemia, as well as improvement in fasting glucose levels in the group with borderline high glucose levels.

Ecuadorian Rainforest’s Mr. Siegel referenced several simple herbal approaches to heart health, clinically proven to offer support. “Green tea is a great ingredient for heart health. According to a study published in the European Journal of Cardiovascular Prevention and Rehabilitation, researchers found that green tea had improved blood vessel function,” he said.

In addition, he cited research lauding the benefits of garlic, stating it helped support healthy blood pressure (Clinical and Experimental Pharmacology and Physiology, 2000) in a rat model, as well as heart rate in a trial examining Rana tigerina frogs (Indian Journal of Experimental Biology, 2004). “Garlic’s antioxidant activity may also boost a healthy heart’s defense,” he said.

The increasingly popular botanical chia offers nutritional support protecting the heart, according to Carolina Chica, RDN, nutrition research and regulatory issues, Benexia, a division of Proprietary Nutritionals. The company’s Benexia Chia ingredients are rich in omega-3s, protein, fiber, antioxidants and minerals (including, calcium, magnesium, iron and zinc), she said. The potent seeds are also free from cholesterol and trans fatty acids.

“The consumption of Benexia chia ingredients, rich in ALA omega-3 fatty acid, dietary fiber and antioxidants, has been associated with decreased levels of blood pressure, lowers LDL (‘bad’) cholesterol, increases HDL (‘good’) cholesterol and reduces triglyceride levels and inflammation indicators (C reactive protein), and coagulation indicators—all of which are risk factors of cardiovascular conditions,” explained Ms. Chica.

Research suggests that chia seeds can increase the omega–3 fatty acid content of animal products such as eggs, poultry meat and cow’s milk, she added. “In addition, the effects of feeding partially ground chia seed and chia oil on rat plasma CHOL, LDL, HDL, TG contents and fatty acid composition was recently reported. The trials showed a dramatic improvement in plasma properties for the rats fed chia, and included decreased triacylglycerol and increased HDL cholesterol contents [Nutrition Research, 2005].”

The grape seed extract, MegaNatural-BP has gone through more than 10 years of research to show it can “maintain healthy blood pressure within the normal range (120/80) with healthy subjects with risk of developing higher blood pressure.” Anil Shrikhande, PhD, president of Polyphenolics, a division of Constellation Brands, Inc., Madera, CA, referenced three different double-blind, placebo-controlled studies examining supplementation with pre-hypertensive subjects in the pre-hypertension range of 120/80 to 139/89. In all the three studies, it was found that daily supplementation of 300 mg of MegaNatural-BP (two with capsules and another with 300 mg low calorie beverage) support healthy blood pressure levels after 4-6 weeks of use.

Discussing these findings, Dr. Shrikhande explained, “The mechanism of action was demonstrated to be upregulation in eNOS, an enzyme responsible for increase in NO [nitric oxide] for increase in endothelium dependent relaxation of arteries thereby reducing the blood pressure to healthy normal range.”

Mr. Anderson of NattoPharma stressed the importance of vitamin K2 in preventing CVD. “According to the World Health Organization (WHO), cardiovascular diseases and osteoporosis are the two biggest global healthcare problems. Vitamin K2 is the last unrecognized vitamin of which most of the population is deficient (at least 97% based on studies measuring the activation of vitamin K-dependent proteins), and this vitamin plays an integral role in bone and cardiovascular health.”

“Vitamin K2 menaquinone-7 (MK-7) has been shown to be a critical vitamin in the calcification factor,” he explained. “Calcium accumulation in arteries is an actively regulated process, strongly influenced by the vitamin K-dependent Matrix Gla Protein (MGP)—the most potent inhibitor of calcification presently known. However, to properly perform its inhibitory function, MGP must be activated by vitamin K2 in a carboxylation (activation) reaction. Vitamin K2 deficiency results in undercarboxylation of MGP, impairing MGP’s biological function.”

He warned that vitamin K deficiency (or insufficiency) could result in inadequate activation of MGP, which greatly impairs the calcium removal process and increases the risk of blood vessel calcification. “Since this process occurs in the vessel wall, it leads to the wall thickening via calcified plaques, which is associated with higher risk of cardiovascular events.”

Mr. Anderson pointed to a study published in Thrombosis and Haemostasis (May 2015), examining 244 healthy post-menopausal women supplemented with 180 mcg of vitamin K2 as MK-7 (as MenaQ7 from NattoPharma). Results demonstrated significant improvement in cardiovascular health as measured by ultrasound and pulse wave velocity (PWV). Ultrasound and PWV are recognized standard measurements for cardiovascular health.

“In this trial, carotid artery distensibility (i.e., elasticity)—the ability for a blood vessel to stretch or dilate—was significantly improved over a three-year period as compared to the placebo group. Also, pulse-wave velocity was significantly decreased in the vitamin K2 (MK-7) group, but not the placebo group, demonstrating an increase in the elasticity. At the study’s conclusion, the Stiffness Index in the MenaQ7 group with initial high arterial stiffness had decreased significantly compared to the slight increase in the placebo group. Results confirmed that a nutritional dose (180 mcg) of MenaQ7 taken daily for three years not only inhibited age-related stiffening of the artery walls, but also made a statistically significant improvement in vascular elasticity.”

Product Innovation
Consumers are looking for ways to seamlessly incorporate heart healthy habits into their daily routine, and in response manufacturers have provided innovative solutions to meet this growing demand.

Mr. Lind of Natreon suggested many research-backed nutraceutical ingredients could seamlessly be infused in a number of convenient and popular foods. “Just looking at the healthy butter/spread market, such as Smart Balance, as one example, we are seeing varieties with added omega-3s, etc.—beverages as well. As the market and demand increases for consumables that protect and nourish the cardiovascular system, consumers will buy those foods and beverages that can add to this protection.” He added that these functional foods and beverages would be a welcome alternative for those consumers suffering from pill fatigue.

However, he said, “It’s very difficult to get the scientifically studied efficacious levels of nutrients in foods without significantly increasing the cost,” making supplements including pills, capsules and softgels the delivery format of choice when it comes to efficacy. “The consumer hasn’t yet shown their willingness to pay the price to get a therapeutic amount of a nutrient in their food. Until that happens, supplements will continue to be the leading application.”

Mr. Anderson of NattoPharma stated that consumers are more inclined to purchase supplements featuring multiple ingredients. “Consumers rarely seek out single vitamins or nutrients. Not only is it not cost effective, but they are looking for combination formulas that work synergistically, and they want their efficacy to be proven.”

For example, he said that omega-3s and vitamin K2 have complementary mechanisms of action, particularly in response to cardiovascular health. With this in mind, NattoPharma obtained a Canadian patent (2,657,748: “Pharmaceutical and Nutraceutical Products Comprising Vitamin K2”; U.S. patent pending) covering pharmaceutical and nutraceutical products providing vitamin K2 in combination with one or more polyunsaturated fatty acids, including fish and/or krill oil, for benefits related to bone, cartilage and the cardiovascular system.

While some consumers look to a pill or capsule, many consumers prefer to get their nutrients straight from the source. This sentiment makes chia seeds a popular item among consumers, according to Mr. Mosca of Proprietary Nutritionals. “Benexia chia seed—as a whole food—is easily incorporated into a variety of convenience foods, adding not only the nutritional profile, but flavor and texture. In and of itself, chia seed can be added to salads, smoothies, breakfast cereals, and even incorporated into healthy breaded meals with whole wheat bread crumbs.”

Market Predictions
With healthcare experts indicating increases among those at risk for CVD, it seems clear the nutraceuticals industry must meet the challenge of serving this large and diverse audience. 

“With the incidence of CVD continuing to rise, and obesity—the leading precursor to this disease—rising precipitously, the need for supplements to combat this disease will continue to rise accordingly,” predicted Natreon’s Mr. Lind.

Horphag’s Mr. Bornet stressed the need for continued research and innovation in the natural products industry, as this level of validation “will become essential for those that seek out the best alternative route for relief of cardiovascular complications.”

He added, “These consumers are becoming much more health-conscious and educated on the ingredients that go into their products and supplements, and will turn to such products that are proven effective to help manage endothelial health and other heart-health related conditions.”

Mr. Siegel of Ecuadorian Rainforest similarly observed the desire among consumers for natural ingredients with fewer side effects preventively addressing heart health issues. “As more people look for supplements, many will stay away from pharmaceutical-like products and look for supplements with ingredients they can pronounce,” he said. “Manufacturers would be wise to market products made with natural ingredients and help inform customers about the benefits they may offer when added to their daily routines.”