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Keeping Rhythm

Heart Health Heart Health

As natural ingredients that address heart health continue to evolve and grow, suppliers are working on broadening awareness.

According to the Heart Foundation, when it comes to heart disease, statistics are still grim:

• Heart disease (including stroke and other cardiovascular diseases) is the No. 1 cause of death in the United States, killing nearly 787,000 people alone in 2011.

• Heart disease is also the leading cause of death for people of most racial/ethnic groups in the U.S., including African Americans, Hispanics and Caucasians. For Asian Americans or Pacific Islanders and American Indians or Alaska Natives, heart disease is second only to cancer.

• Cardiovascular diseases claim more lives than all forms of cancer combined.

Heart disease is clearly a public health concern, especially for the aging population. However, for children and young adults, obesity and added sugars are proving to pose risks for future heart disease. According to Annie Eng, CEO of Florida-based HP Ingredients, the state of the market for natural ingredients that address heart health continues to grow rapidly. “Many young adults today grew up with very poor diets, setting the stage for high numbers— cholesterol, blood pressure, blood glucose, and many are overweight. In short, from today’s young adults through older middle-age, many American consumers are dealing with metabolic syndrome and its companion condition, non-alcoholic fatty liver disease (NAFLD).”

To a significant degree, future heart problems, such as CVD (cardiovascular disease), can be largely prevented, barring the existence of genetic predispositions or congenital conditions, the earlier an individual adopts a healthy lifestyle, Eng added. “Millennials are definitely getting the message, and this generation appears to be much more health-conscious and willing to be preventative than any other previous generations. This bodes very well for the market.”

Aparna Kalidindi, PharmD, BCPS, technical sales and marketing manager with Natreon, Inc. in New Jersey, pointed out that the heart health supplement category came in at $2.4 billion in 2015. “Total supplement sales have been steadily increasing since 2004,” she said. “With pharmaceutical agents like statins under fire, consumers are looking for new heart health supplements. Several supplement companies have launched new heart health supplement lines, as fish oil sales decline due to several studies questioning their efficacy.”

And, according to Golan Raz, vice president of health and nutrition at New Jersey-based Lycored, the market for heart health maintains its normal “BPM” with minor yet solid year over year growth. “We see a growing interest in new technologies (compositions) that are designed to support multiple cardiac needs and risk factors,” he said, “and at the same time, a decline in the demand for ‘marker’s specific’ ingredients like cholesterol management agents.

“Furthermore,” he said, “we see a deeper interest from leading brands as well as consumers in fully validated products that can provide solid scientific support to the efficacy of the finished product and not just to a single ingredient.”

Array of Ingredients

A large assortment of natural ingredients that support heart health exists. “The most successful ingredients in the marketplace are clinically tested in one or more human clinical trials,” said Bruce Abedon, PhD, vice president of scientific affairs with NutraGenesis/Icon Group in Vermont.

Despite recent questions regarding efficacy, Hugh Welsh, president of DSM North America in Georgia, maintains that the most important ingredients in the heart health category are EPA and DHA omega-3 fatty acids. CoQ10 and fibers are also products that consumers purchase, he noted. “EPA and DHA supplements are typically labeled as ‘fish oil’ and more needs to be done by the industry to educate consumers to look for the EPA and DHA content in the fish oil they choose. The largest part of the category volume is driven by men 50 plus, but many women also consume these products.”

Becky Wright, marketing and communications director—Superba, with Aker BioMarine Antarctic US in New Jersey, agreed that for omega-3s, “in a nutshell, research shows that omega-3s maintain blood pressure and cholesterol levels (within a normal range), help promote a regular heart rhythm and support normal blood clotting processes, all helping to keep both the heart and its arteries healthy. Taking that a step further, EPA and DHA omega-3s help reduce risk of cardiac death, maintain healthy blood pressure levels, and keep triglycerides within normal range. In fact, EPA/DHA are among the most researched nutrients in the world.”

Also supported by science and well-known heart health ingredients are phytosterols and tocotrienols, said Bryan See, regional product manager with New Jersey-based ExcelVite.

Natreon’s Capros, a “super” antioxidant, is said to support healthy blood flow and healthy cholesterol levels. “In addition, more younger athletes and ‘weekend warriors’ are also taking these supplements for better performance (improved endothelial function/nitric oxide boosting),” Kalidindi said.

“Lycored Nutrient Complex for Heart (Cardiomato) won an award for [finished] product of the year and that achievement is a wonderful recognition of the industry for Lycored’s ongoing commitment to research and development,” Raz noted. “Another good product,” he added, “is FruitFlow by DSM. This is an interesting technology that focuses on the improvement of platelets aggregation and blood flow. We also see the more traditional ingredients like CoQ10 preforming in a solid way.”

Missouri-based DuPont Nutrition & Health markets SUPRO brand isolated soy proteins, which have been shown in clinical research to have a positive effect on elevated cholesterol levels, said Jean Heggie, strategic marketing lead. “In fact, that research formed the basis of soy protein and heart health claims that are now in place in 11 countries around the globe. Soy protein is the only protein source approved for such a claim. In the U.S., manufacturers who include 6.25 grams of soy protein per serving in their product and meet other nutritional criteria on fat, saturated fat and cholesterol, can include a claim on their labels linking soy protein to reduced cardiovascular disease risk.”

Ingredient Evolution

Alongside launches, suppliers have noted the evolution of key heart ingredients. Some include:

• Bergavit 40, sold by NutraGenesis, is derived from the fabled, heart-healthy Bergamot citrus fruit (Citrus bergamia). It has been evaluated in human clinical trial testing and possesses flavonoid bioactives that help support healthy blood lipid levels, as well as the quality of blood lipid types, and that also help improve carotid intima-media thickness. This ingredient is a more concentrated form of a previously sold ingredient so requires a lower clinically efficacious once daily dose.

• WellTrim iG, a clinically tested African Mango extract, and Synetrim CQ are marketed by Icon Group. These are weight management nutraceuticals that also provide significant metabolic wellness benefits in the area of cardiovascular health. Each has been evaluated in multiple human clinical trials using either once daily or twice daily dosing, which has resulted in significant support of healthy blood lipid levels in addition to improvements in weight. Both ingredients help support cardiovascular health through antioxidant properties and other mechanisms.

• DSM’s Meg-3 just launched a new technology called 3C, which stands for concentrated, customized and consistent. It allows supplement companies to innovate with high concentration EPA and DHA products—up to 85 percent—with economics that make standard fish oil a thing of the past. It also allows customization of the ratio of EPA to DHA, so that a brand could innovate for example with an EPA only supplement for heart health. This technology also reduces dependency on the omega-3 content of the fish allowing for diversification of the fish oil supply chain to provide a sustainable operation without interruption risk because of weather patterns disruption some regional fisheries.

• Another bergamot ingredient, HP Ingredient’s Bergamonte, contains bioactive compounds of extract of the juice and albedo of Citrus bergamia Risso, standardized to >38 percent polyphenolic flavonoids consisting of naringin, neohesperidin, neoeriocitrin, 1 percent melitidin, and 2 percent brutieridin. It is produced using patented extraction technology through collaborative works of various universities and research institutions in Italy.

Bergamonte has been found to help balance many of the risk factors of metabolic syndrome and attendant NASH (nonalcoholic steatohepatitis); NASH has been identified as the hepatic manifestation of metabolic syndrome. Recent evidence shows that Bergamonte, when consumed by individuals with metabolic syndrome and NASH induces a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol. In addition, a significant reduction of both ultrasonographic, TC scans and metabolic biomarkers of NASH as well as a significant reduction of small dense LDL particles were found after Bergamonte treatment suggesting a beneficial effect of bergamot-extract in individuals with metabolic syndrome and NASH. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.

• ExcelVite’s EVNol SupraBio is a natural full-spectrum tocotrienol complex with patented self-emulsifying delivery system, specifically developed to provide consistent and enhanced oral absorption of each individual tocotrienol isoforms. The SupraBio system is formulated with a proprietary blend of oil and food emulsifiers at an optimum ratio and homogenization process that will self-emulsify in the gastrointestinal tract that facilitates absorption. Further physiological processes generate conditions essential for optimal absorption of each isoform of tocotrienols into the plasma. This novel delivery system results in a rapid and consistent absorption of tocotrienols independent of dietary fat or food intake. Pharmacokinetic study with healthy human volunteers confirmed the efficacy of the SupraBio system, which increases the rate and absorption of each individual tocotrienols by up to 300 percent (average 250 percent) (Ho D, et al., 2003), compared to a conventional, non-bioenhanced tocotrienol oil extract.

• Natreon’s Capros is a super antioxidant (ORACFN of 47,000 µmoles TE/g) and an excellent cardiovascular product derived from the edible fruits of Phyllanthus emblica. It is an aqueous extract, vegetarian, organic, non-GMO (genetically modified organism), kosher and halal with a no objection GRAS (generally recognized as safe) letter from the FDA (U.S. Food and Drug Administration). The efficacy of Capros is backed by multiple clinical studies, many of which have been published in peer reviewed journals. Capros is soluble and stable in solution, making it ideal in ready to drink beverages. In addition, Capros can be offered in a small dosage form, thus increasing consumer compliance, unlike fish oil products, which are large and often have an unpleasant aftertaste. Capros activates eNOS, which results in increased production of nitric oxide and thereby improving endothelial function.

• Natreon’s Crominex 3+ is a trivalent chromium supplement that offers cardiovascular and blood glucose support. It is prepared by complexing chromium chloride with two natural products, Phyllanthus emblica (Natreon’s Capros) and Shilajit (Natreon’s PrimaVie) in order to minimize conversion conversion of chromium III to chromium VI and to increase bioavailability. This complex produces significant synergistic activity. Crominex3+ is water soluble, manufactured by a completely aqueous extraction process in the US, and kosher/halal certified.

• Lycored Nutrient Complex for Heart (Cardiomato), was proven to support healthier post-meal fats and sugars management. Demonstrated in well-controlled clinical trials with over 150 healthy subjects, one soft gel a day of Lycored Nutrient Complex for Heart (Cardiomato), reduced post prandial Ox-LDL levels and supported improved blood sugar levels, triglycerides and insulin resistance all within the normal range. Lycored research teams demonstrated in both pre-clinical and clinical trials, that this innovative technology activates NRf2 as well as NFkB related process and by doing that, reduces Ox LDL levels, manages blood pressure in the normal range and supports health endothelial function.

• Aker BioMarine’s flagship product Superba Krill is rich in phospholipid omega-3s EPA and DHA, important nutrients for a healthy heart. Scientists have proposed several different mechanisms by which phospholipid omega-3s promote cardiovascular health and since phospholipids assist in the more efficient cellular uptake of omega-3s, they deliver EPA and DHA to the places your body needs them the most, plus they are more readily absorbed by the body.

Superba2, the next generation of Superba Krill Oil, featuring a new and improved formulation with enhanced encapsulation properties such as improved smell, taste and visual appearance. Superba Boost, Aker’s newest product, is a krill oil concentrate, which contains a significantly higher concentration of key actives, including phospholipids, omega-3s EPA/DHA and choline.

Effective Delivery

Delivery, of course, depends very much on the nature of the ingredients. “Take phytosterol as example,” said See. “The recommended delivery system is through food such as bread spreads. For other oil soluble ingredients such as CoQ10, omega-3s and tocotrienols, the preferred delivery system is generally through soft- or liquid-capsule dosage forms.

“Although consumer can obtain these ingredients naturally through food (like fish for omega 3), one must consume a large quantity of that food to obtain sufficient amount of ingredient that has been shown to bring about benefits,” See added. “Tocotrienol is scarce in nature. While palm oil is the most abundant source for tocotrienols, one has to consume 80 g of palm oil to attain the 30-50 mg tocotrienols recommended for general wellness, including heart health, hence it is not a practical way of consumption due to the high calorie intake from the oil. As a result, the cost effective and healthy way to consume tocotrienols is through soft gel dosage form.”

In addition, traditionally, EPA and DHA omega-3 have been delivered in the supplement industry in the form of soft gels to allow for a relatively high dose that meets the recommended level by world organizations for healthy consumers, said Welsh. “The market has experienced growth in the last few years with gummies which typically deliver about a third of the dose of a soft gel for that ingredient,” he said. “The industry should consider opportunities to deliver new forms to delight the consumer: an example could be a deliciously creamy smoothie like formula in which the amount of EPA and DHA per dose could be triple that of a soft gel.”

If the ingredient is water soluble, other novel delivery forms are available, such as stick packs, dissolvable strips, or liquid products such as shots or beverages. NutraGenesis/Icon Group’s Bergavit 40, WellTrim iG, and Synetrim CQ work well with these traditional and non-traditional delivery vehicles since they are all water-soluble.

As for MenaQ7, yogurt is a very effective delivery system, as shown in studies, said Anderson. A 2015 study that was published in The Journal of Nutritional Science, adds to the growing body of evidence that vitamin K2 is a safe and effective supplement. A yogurt drink fortified with menaquinone-7 improves vitamin K status in healthy populations.

Research of Interest

Human clinical trials are the most reliable measure of a cardio health product’s efficacy and safety profile. The best products use ingredients that have been evaluated using a “Gold Standard” protocol that includes randomization, double-blinding, and comparison to a placebo.

Raz added that trials should be well-controlled, performed in recognized medical centers and led by qualified specialists. “Furthermore, we see a great interest in the statistical power of the studies with a growing understanding among all parties involved (brands, manufacturers) to the importance of the target population on which the study was performed.”

Scientific research conducted in humans with positive outcomes in cholesterol management usually interests suppliers, manufacturers and consumers, according to See.

Also, Eng noted that research into the link between NAFLD and metabolic syndrome, and what ingredients can effectively provide protection against these conditions will be of significant importance to the cardiovascular support category.

Soy Research on Cholesterol

More human clinical studies have been conducted to assess the hypocholesterolemic effects of soy protein than any other cholesterol-lowering food ingredient, said Michelle Braun, PhD, research scientist with DuPont Nutrition & Health. “Multiple meta-analyses have been conducted confirming the cholesterol lowering efficacy of soy protein. There is interest in directly measuring not only risk factors for disease but the occurrence of the disease or its progression.”

Braun pointed to a large prospective population study, The Shanghai Women’s Health Study, which showed that women in the highest tertile for soy protein consumption had a 75 percent lower risk for coronary heart disease and an 86 percent lower risk for non-fatal myocardial infarction compared to the lowest tertile over a three-year follow-up period (p<0.003 for the trend). Whether this reduction in cardiovascular events was due to soy protein’s cholesterol-lowering effect or other properties remains to be determined.

A controlled clinical study recently was able to investigate disease progression. Hodis et al. quantified the progression of intima-media thickness (a measure of atherosclerosis) in the carotid artery of post-menopausal women over a 2.7-year period. Although there was a non-significant (P=0.36) 16 percent decrease in the progression of intima-media thickness in the women who consumed 25 g/day soy protein, a subset of the women who were within five years of menopause onset showed a 68 percent lower carotid intima-media thickness (insert p value) progression rate compared to women consuming an equivalent dose of milk protein.

Working Ahead

Oil or fat-soluble ingredients and certain botanical extracts that are insoluble at all, pose the most challenges in processing and formulating, according to See. “Very often, these ingredients are poorly absorbed or not absorbed at all. The tocotrienol is one such ingredient because vitamin E is a fat-soluble compound.”

The oral bioavailability of tocotrienol is low and erratic by nature, he added. “To improve absorption, a person will need to consume tocotrienol after a meal consists of oily food. Under this situation, although the amount of tocotrienol being absorbed is increased, the level absorbed is inconsistent and varies according to the amount and type of fats that has been consumed.”

The formulation challenge with tocotrienol lies in the need to ensure consistent and high absorption so that consumers really receive the optimal level of tocotrienols that show benefits in research. Hence, the trend in the industry is moving towards “bioavailability,” ie., absorption into the blood plasma.

It doesn’t just end at or with absorption/bioavailability, according to See. The next big trend in the industry is “bioefficiency”—the accumulation or deposition of an active phytonutrient into various vital human organs.

To spread the word and help educate medical professionals on the high cardiovascular risk that the U.S. population is developing with its unhealthy lifestyle and diet choices, DSM developed a campaign called “Know Your O” (www.knowyouro.com). This campaign aims at developing the awareness of HCP’s on the U.S. population omega-3 status deficiency, how much omega-3 to recommend to a patient, what type of fish they should eat and how to select a good omega-3 supplement for those who do not or cannot consume enough omega-3 from diet alone.

“DSM is looking for consumer brands interested in joining this effort among doctors,” said Welsh. “There is a tremendous opportunity to make the U.S. consumer healthier through this initiative, drive category growth, and gain a disproportionate share for the marketers willing to place their brands in the center of this initiative and in the doctor’s office.” NIE

Sidebar:

Vitamin K Update

NattoPharma USA (New Jersey) is making strides in the heart health market with its MenaQ7 product. Since it was first introduced, novel technologies have been pioneered to expand the product portfolio, said Eric Anderson, senior vice president global sales and marketing.

The MenaQ7 product range caters to a growing global demand of high-purity, stable and well-researched vitamin K2 as MK-7, and is offered as a naturally fermented ingredient (MenaQ7 Crystals) or a nature-identical synthetic ingredient (MenaQ7PURE), in multiple dilutions and solubilities, according to Anderson.

NattoPharma’s MenaQ7 Crystals represents a significant development of the vitamin K2 product line offering documented health benefits. The most substantial technological development in the new generation of MenaQ7 products is a proprietary multi-step process of purification, condensation, and crystallization of naturally derived vitamin K2. This innovative process leads to an end product that is more than 96 percent pure natural menaquinone-7 (MK-7). Further, as it is manufactured using Bacillus licheniformis in a non-soy based medium, MenaQ7 Crystals is free of soy products and all known allergens.

“Consumers vary widely,” Anderson added, “from kids who should be consuming K2, to young adults who want to maintain healthy cardiovascular function, to those in middle-age and elderly active individuals who are very concerned about not having heart issues.”

References:

Gliozzi, M. et al., The effect of bergamot polyphenolic fraction in patients with non-alcoholic liver steato- hepatitis and metabolic syndrome, PharmaNutrition (2015),

Gliozzi, M., et al. (2014) The Effect of Bergamot-Derived Polyphenolic Fraction on LDL Small Dense Particles and Non Alcoholic Fatty Liver Disease in Patients with Metabolic Syndrome. Advances in Biological Chemistry, 4, 129-137.

Zhang X, Shu XO, Ga Y-T, Yang G, Li Q, Honglan L, et al. Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. The Journal of Nutrition. 2003;133:2874-2878.

Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, et al. Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: A randomized controlled trial. Stroke. 2011;42(11):3168-3175.

Ajuluchukwu JN, et al. (2007). Comparative study of the effect of tocotrienols and alpha-tocopherol on fasting serum lipid profiles in patients with mild hypercholesterolemia: a preliminary report. Niger Postgrad Med J., 14 (1), 30-3.

Ho D, et al. (2003). Drug delivery system: formulation for fat soluble drugs. U.S. Patent No. 6,596,306.

Patel V, et al. (2012). Oral Tocotrienols are Transported to Human Tissues and Delay the Progression of the Model for End-Stage Liver Disease Score in Patients. The Journal of Nutrition, 142 (3), 513-9.

Rasool AHG, et al. (2008). Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res Vol , 31 (9), 1212-1217.

Yuen KH, et al. (2011). Effect of Mixed-Tocotrienols in Hypercholesterolemic Subjects. Functional Foods in Health and Disease, 3, 106-117.

For More Information:
Aker BioMarine, (732) 860-0137
DSM, www.dsm.com
Dupont, www.dupont.com
ExcelVite Inc., (732) 906-1901
HP Ingredients, (877) 437-2234
Lycored, (973) 672-2160
Natreon, (732) 296-1080
NattoPharma, (609) 454-2992
Nutragenesis/Icon Group, (802) 257-5345

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