Alissa Marrapodi

September 5, 2011

21 Min Read
Heart Health: Unsaturated Facts

The heart really is the heart of the bodys whole operation. Without it, everything else ceases to work. But when the heart works overtime, things can go wrong. And unfortunately, many Americans hearts are on overdrive.

Cardiovascular disease (CVD) kills more people worldwide than any other disease, said Stephen Moon, CEO, Provexis plc. Indeed, experts estimate by the year 2020 nearly 40 percent of all deaths worldwide will be due to CVD, more than twice the percentage of deaths from cancer [according to a study published in the New England Journal of Medicine]. Governments, health professionals and health-oriented media have consistently pressed the message on the importance of cardiovascular health, leading to increased consumer awareness of the consequences of CVD. He sees consumers being proactive and adding supplements and functional foods and beverages to support their heart. The statistics support this view, with the U.S. heart-health market projected to exceed $1 billion by 2012 and $2 billion by 2015, he added.

The heart-health market is a fortunate one: It doesnt suffer from saturation due to bogus claims and promises. In fact, its a fairly clean market. I definitely agree with the statement that the heart-health market doesnt seem to be saturated with claims that other markets suffer, said Dave Foreman, RPh, N.D. I believe this is because heart health is a lot more life threatening than weight loss and arthritis. Companies would be seriously compromising the customers health if they were to make crazy, undocumented claims about their products/ingredients.

Why else is this a cleaner market? Marketing, and regulatory checks and balances. Heart health targets a very different demographic than say, weight management, which suffers from market saturation partly due to fads and over-the-top claims. Taking supplements for the heart isnt done out of vanity, it stems from a need and a genuine desire to be healthy. The weight loss/management market is saturated with fad products that do whatever is necessary to stand out from the crowd, and is targeted primarily toward young women, said Jeremy Bartos, Ph.D., ingredient product manager, pTeroPure division of ChromaDex Inc. The heart-health market targets a different demographic than weight management; older men and women not as easily drawn in to impulse buying of fad products, and are more likely to consult a physician or research products before committing to buy. Because of this, the heart-health market relies more on the science to sell products, as science and clinical data is what is needed to get a physician to recommend a product to their patients.

The heart-health market adheres to strict regulations that are continuously increasing. Claims are limited to supports a healthy heart or supports normal cholesterol levels already in the normal range, which may not be eye-catching to consumers, Paul Dijkstra, CEO, InterHealth Nutraceuticals, noted. Heart-health ingredients with unique claims based on mechanism of action and superiority claims may help differentiate a product in the marketplace.

So, do consumers really understand and comprehend what a healthy heart needs? Foreman graded consumer awarenessfrom his experience hosting his radio program and from participants during seminarswith a mediocre C+. As most are aware of using omega-3s and maybe coenzyme Q10 (CoQ10), they often get confused about the exact amounts to use to be effective, he said. The time that I run into someone who knows about other heart-health ingredients is when they have a specific serious need such as high blood pressure, stroke, etc. Then, these consumers often grade at about B+ because they are more concerned about more serious consequences such as stroke or death.

Dijkstra couldnt agree more. Consumers may be hearing the message, but its obvious many are still not making the necessary lifestyle changes needed to maintain their heart health, he said. Consumers may know, to some degree, they should supplement with a heart-health product; however, consumer awareness as to the specific benefits of specific ingredients, even ones as popular as omega-3s and CoQ10, may not be as great as many of us would like to think.

Consumers may not be heart-health brilliant, but they do make some associations between the heart and omega-3s. Patrick Luchsinger, industry specialist, Stepan Lipid Nutrition, highlighted the recent launch of a CoQ10 functional beverage (milk) with the addition of omega-3s, mainly because of consumer recognition, even though both ingredients can help support heart health. According to the Natural Marketing Institute (NMI) 2009 & 2010 Health and Wellness Trends Database, more than half the U.S. population associates omega-3s with heart-health benefits. With numbers like that, milk may want to switch their campaign to Got Omega-3s?

But Foreman has a point: Even though the heart-health market is hearty, it still reserves some room for growth. NMIs 2010 Health & Wellness Trends Database reported only 8 percent of consumers associate plant sterols and resveratrol with heart health. Moreover, NMIs research found only 19 percent of consumers indicated they take a supplement specifically for heart health, and 10 percent of consumers indicate they or someone in their household is actively managing/treating heart disease.

The supplement industry simply needs to do more consumer promotion, said Anil Shrikhande, Ph.D., president, Polyphenolics. Nearly everyone knows one of the key indicators of a healthy heart is healthy blood pressure. But do they know what exactly blood pressure is and why is it so important? Im not so sure the average consumer knows this.

Whats interesting when evaluating the research related to all matters of the heart is theres a strong correlation between dietary choices and heart health, e.g., fish, fruits and vegetables, wine and nuts. Many ingredients and raw materials designed for heart-health products are available in the grocery (nuts, fruit, olive oil and fiber), seafood (omega-3s) and alcohol (wine) aisles. But more often than not, although these foods are easy to incorporate into an everyday diet, they are not as nutrient-dense or potent coming from the shelf as their supplement or fortified-food and -beverage counterparts.

The American Diet Gone Mediterranean

The Mediterranean diet has long been revered for its nutrient dense foods. While the Western diets stigma stings the heart, Mediterranean staples such as olive oil, and fruits and vegetables, nuts, wine, fish and fiber soothe the heart. One of most heart-healthy diets ever studied, the Mediterranean diet, contains several ingredients that reduce oxidized low-density lipoprotein (LDL) cholesterol, including olive oil, tomatoes and mushrooms, said Joseph L. Evans, Ph.D., manager, pharmacology and Novus Research fellow, Stratum Nutrition .

Two Spanish studies highlighted its role in heart health: one found a statistically significant interaction between olive oil intake, and fruit and vegetable consumption in relation to hypertension;1 while the other found two versions of the diet containing either nuts or virgin olive oil decreased LDL, concluding the diet may be a useful tool in combating coronary heart disease (CHD).2

Evans recently published research also adds confirmation to the findings above, as olive extract, lycopenethe carotenoid responsible for tomatos red coloringchitin-glucan and green tea reduced oxidized LDL, a proatherogenic mediator and biomarker for CVD.3 Evans noted his current research is focusing on the clinical evaluation of a novel fiber derived from a mushroom, which has been shown in animal studies to prevent atherosclerosis and in humans to lower oxidized LDL.

Additional research on tomatoes, including their whole form and lycopene, has outlined their ability to fight free radicals and manage cholesterol. One study published in Nutrition, Metabolism and Cardiovascular Disease showed lycopene is not only a potent antioxidant, but tomato phytonutrients render LDL cholesterol 90-percent more resistant to oxidation than LDL alone.4 An Israeli study found whole-tomato extract (as Lyc-O-Mato®, from LycoRed) has a beneficial effect on blood lipids, lipoproteins, oxidative stress markers, and has the ability to lower blood pressure at levels comparable to conventional treatment.5  

In addition to quenching free radicals, studies have demonstrated supplementation with Lyc-O-Mato may be associated with a reduction in systolic and diastolic blood pressure, said Steve Holtby, president and CEO, Soft Gel Technologies Inc. (SGTI), which offers softgels with Lyc-O-Red.

According to two studies published in the American Journal of Clinical Nutrition, Fruitflow® (from Provexis), a patented extract from ripe tomatoes, also showed its potential role in primary prevention of CVD by reducing platelet activation.6,7 Fruitflow helps maintain a healthy cardiovascular system by smoothing blood platelets and helping to decrease blood platelet aggregation, Moon said. Published clinical studies have demonstrated Fruitflow reduces platelet aggregation in 97 percent of individuals within 1.5 hours of consumption and its beneficial effect lasts up to 18 hours.

From one vine to the next, resveratrol, grape seed extract (GSE) and pterostilbene, all found in grapes, as well as other fruits and vegetables, are major players in this category. A wealth of new research findings continue to underscore the wonders of resveratrol, which has been shown to significantly impact the aging process, regulate for positive cardiovascular function, and protect against and reverse cancer, Holtby said. Its achieved superstar status, thanks to the promotion of this anti-aging supplement by Dr. Oz.

But the three ingredients are quite different. GSE supports healthy blood pressure. Two placebo-controlled human clinical trials conducted by researchers at the Department of Preventative Cardiology, University of California Davis School of Medicine, have found MegaNatural®-BP supports blood pressure within the normal range, Shrikhande noted. A 2009 study that randomized subjects into three groups(a) placebo, (b) 150 mg/d of GSE and (c) 300 mg/d of GSEfor four weeks, found both the systolic and diastolic blood pressures were lowered after treatment with the grape seed extract as compared with placebo.8

Pterostilbene is like resveratrol, as its a natural stilbenoid found in small berries such as blueberries and grapes, and both are phytoalexins (chemicals that are part of the plants defense system and are produced when the plant is under attack by pathogens such as bacteria or fungi. However, they are different, too. One of the major differences is pterostilbene contains two methoxy groups and one hydroxyl group, causing it to be more oil soluble, while resveratrol has three hydroxyl groups.9,10

Pterostilbene has been shown to reduce LDL cholesterol and raise the good HDL.11,12 Bartos said pterostilbene functions as a PPAR alpha activator. As a PPAR alpha activator, it works to reduce the bodys production of LDL cholesterol and triglycerides while also raising HDL levels, he said. Pterostilbene has also been shown in animal models to reduce the risk of atherosclerosis by inhibiting the proliferation of vascular smooth muscle cells and its been shown to up-regulate endothelial nitric oxygen synthase (eNOS), which acts to increase vasodilation and lower blood pressure.

He also highlighted an interesting shift in current research: We see the trends are changing from familiarity with general ingredients to specific heart-health problems and the science behind treating them, he said. In that respect, these new trends are about utilizing a pharmaceutical approach to first research the science behind the disease of interest and then determine which nutraceutical ingredients or products would target the particular need. Which pterostilbene has undergone, outperforming drugs targeting the same pathway, both in cholesterol and in type 2 diabetes. Currently, ChromaDex is sponsoring a human clinical trial on pterostilbene at the University of Mississippi, focusing on pTeroPures ability to lower LDL cholesterol and blood pressure, as well as raise HDL cholesterol.

Pairing your wine with a synergistic snack may be the way to a healthy heart, because nut allergy or not, nuts are a staple in the Mediterranean diet; and for those who can stand the crunch, nuts nutrient-diverse profile offer hearty benefits. While typically placed in the food category, I think it is only a matter of time until we start to see nut-derived supplements (e.g., extracts, single ingredients), since the evidence for the consumption of almonds, walnuts, Brazil nuts, cashews, peanuts, pistachios and pine nuts and the reduced risk for CVD is very compelling, Evans said. Nuts contain compounds that lower cholesterol and blood pressure, both validated risk factors and surrogate end points (can be used in clinical studies in place of actual outcome measurements) for CVD.

Researchers found pistachios, when consumed as a portion-controlled snack, dont pack on the pounds, and when compared to refined carbohydrate snacks such as pretzels, pistachios may also have beneficial effects on triglycerides.13 Additionally, a study published in the European Journal of Clinical Nutrition said pistachios effect on post-meal glycemia could reduce the risk of diabetes and CHD.14 The American Diabetic Association (ADA) conducted a study on almonds, finding these nuts yielded clinically significant improvements in LDL cholesterol in adults with prediabetes.15

Chocolate is another healthy companion to wine. Cocoa has been shown to decrease cholesterol,16 lower blood pressure, improve the health of blood vessels and increase the number of circulating angiogenic cells in patients with coronary artery disease (CAD).17 High-flavanol cocoa (as CocoaVia, from Mars Inc.) was found to improve endothelial function18,19, 20 and induce vasodilation by activating the nitric oxide system.21  

Fiber is another staple in the Mediterranean diet. An insoluble fiber, Artinia (from Stratum Nutrition), isolated from Asperfillus niger, has worked a number on the heart. Studies support its ability to reduce oxidative stress and triglycerides, and block aortic plaque development by 95 percent22; reduce LDL by 26 percent;23 and decrease high-fat diet-induced body weight gain, fat mass development, fasting hyperglycemia, glucose intolerance, hepatic triglyceride accumulation and hypercholesterolemia.24

From fiber to fish, omega-3s need no introduction. In the past six months, more than 300 products containing DHA have launched across several categories, including food and beverage and supplements, said Anthony Martin, manager, public relations, Martek. Numerous scientific studies confirm that everyone, from infants to adults, benefit from an adequate supply of DHA throughout life. From EZ Mega 3 from SGTI to LifesDHA plus EPA from Martek, part of DSM, the word is out about omega-3s.

A different source of DHA and EPAand not as well-known as fish oilis krill oil. Krill oil is the fastest growing omega-3 category thanks to three primary factors: tolerability, bioefficiency and sustainability, said Eric Anderson, vice president of sales and marketing, Aker BioMarine Antarctic US Inc. A study published in the Journal of Agricultural and Food Chemistry found krill oil (as Superba Krill Oil, from Aker BioMarine) reduced the level of cholesterol in the blood.25 Whats interesting to note is, according to a study published in Lipids, plasma EPA and DHA levels increased in subjects supplementing with fish oil or krill oil equally; however the krill oil supplement (from Aker BioMarine) had 62.8-percent less (543 mg/d of EPA + DHA) than the fish oil (864 mg/d of EPA+DHA).26 The same study also showed krill oils was 4.3 times more effective than the omega-3 concentrate in raising plasma HDL cholesterol levels, and 14.9 times more effective in decreasing triglyceride levels.

CoQ10, Tocotrienols and Minerals

As mentioned earlier, CoQ10 is a popular choice in the management of a healthy heart. According to Global Industry Analysts (GIA), more doctors are recommending it, contributing to industry projections of a global rise that will exceed $133.3 million by the year 2015.

Recent research found CoQ10 in its reduced formubiquinol (from Kaneka)reduced the LDL cholesterol of healthy men after two weeks of supplementation, according to a recent German study.27 And a combined effort from Pycnogenol® and Kaneka (as PycnoQ10®, distributed by Horphag Research USA) improved heart failure management without side effects when stable heart failure patients took the supplement in adjunct to medical treatment.28 

SGTI offers three forms of CoQ10: CoQsol®an all-natural, enhanced-absorption, soft-gel formulation of CoQ10 with beta-carotene and mixed tocopherols; CoQsol-CF®a crystal-free soft gel CoQ10 formulation thats completely solubilized; and CoQH-CF®a soft gel delivery system with Kaneka QH that helps increase plasma levels of CoQ10 for those who have difficulty processing CoQ10.  

From one lipid to the next, palm tocotrienols from the vitamin E family work on a number of heart-health issues. They have been shown to regress atherosclerosis,29 reduce cholesterol levels30 and lower systolic blood pressure.31 One study showed six months of supplementing 300 mg/d of a bioenhanced palm mixed tocotrienol complex (as Tocomin SupraBio® from Carotech Inc.) significantly reduced total cholesterol and LDL cholesterol concentrations in humans with high cholesterol levels.32 And a separate study showed Tocomin SupraBio reduced arterial stiffness after two months of supplementing 100 to 200 mg/d.33

It is important to understand not all tocotrienol is created equal, said Bryan See, regional product manager, Carotech Inc. There are other sources of tocotrienol that claim to be beneficial to the heart, but they are using scientific results borrowed from palm tocotrienol complex.

From chromium to magnesium, minerals are essentials to the hearts functionality. A study conducted at Georgia Southern University, Statesboro, found chromium (as ChromeMate®, from InterHealth Nutraceuticals) decreased mean total cholesterol.34 Low levels of magnesium have been shown to accelerate atherogenesis by increasing LDL concentrations and their oxidative modifications, and the promotion of inflammation.35 When compared to fish oil, magnesium (as Magnesium Amino Acid Chelate, from Albion Minerals) causes a significant decrease in platelet aggregation and afforded a complementary vasodilatory effect.36

New Matters of the Heart

Sure heart health has its old timers and staples, but there is also a lot of innovation happening, too. Less developed, but highly lucrative is the medical foods sector, focusing on the non-invasive treatment of clinical diseases, Moon pointed out. Provex is interested in bridging the gap between functional foods and medical foods sectors. The company is conducting research on cardiovascular inflammation in collaboration with the Institute of Food Research in Norwich, U.K. Cardiovascular inflammation is a highly serious condition, as it plays a role in all stages of atherothrombosis. Research has shown this to be the underlying cause of approximately 80 percent of all sudden cardiac death cases. Provexis has identified isothiocyanates contained in certain cruciferous vegetables such as broccoli, mustard seeds and watercress have a positive effect on heart health. Preliminary clinical trials are now underway to establish effective dosage of the extract. Formulation will then be refined ahead of human trials planned as part of a cardiovascular inflammation study next year. The ingredient currently exists as a freeze-dried powder for eventual incorporation into dietary supplements, with a liquid format suitable for beverage applications also a potential solution.

Anderson highlighted some new research revealing krill oils benefits in the endocannabinoid system. Endocannabinoids are involved in things like hunger and mood and other fundamental systems, he said. Krill oil supplementation seems to encourage the body to express visceral fat, fat that is around the organs, and also to lower triglyceride blood levels. This is a very new, exciting area with significant implications for things like metabolic syndrome and obesity; and this is just getting started.

Luchsinger said hes noticed an emergence of several new ingredients, including seaweed, soy protein, vitamin K2 and tocotrienols.

One of the new categories of cardiovascular health compounds are dairy-derived peptides and polypeptides, Dave Pfefer, product manager, fortification, Caravan Ingredients, added. These have shown various degrees of blood pressure reduction and are considered to be more all-natural then the pharmacological drugs.

Innovation and education are key in this market. The industry is hard at work researching innovative ingredients; but its clear consumers still to be educated on all matters of the heart beyond CoQ10 and omega-3s.

References are on the next page...

References for Heart Health: Unsaturated Facts

1.       J M Nuñez-Cordoba et al. Role of vegetables and fruits in Mediterranean diets to prevent hypertension Eu J Clin Nutr. 2009;63:605612

2.       Montserrat Fitó, M.D., Ph.D., et al. Effect of a Traditional Mediterranean Diet on Lipoprotein Oxidation Arch Intern Med. 2007;167:1195-1203

3.       Joseph L Evans. Cardiovascular Health Benefits of the Mediterranean Diet Targeting oxidized LDL Agro Food Industry 2011;40-2

4.       Giugliano Dl. Dietary antioxidants for cardiovascular prevention Nutr Metab Cardiovasc Dis. 2000 Feb;10(1):38-44

5.       Engelhard YN, Gazer B, Paran E Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study Am Heart J. 2006 Jan;151(1):100

6.       Niamh OKennedy et al. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans Am J Clin Nutr. 2006;84:5619

7.       Niamh O'Kennedy et al. Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans Am J Clin Nutr.  2011;5:182-191

8.       Brahmesh Sivaprakasapillai et al. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome Metabolism. 2009 Dec;58(12):1743-6

9.       S. Hougee, et al. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers Planta Med. 71, 387 (2005)

10.   M. Cichocki, et al. Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFkappaB, AP-1, COX-2, and iNOS in mouse epidermis Mol. Nutr. Food Res. 2008;52,S62

11.   Mizuno CS et al. Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha Bioorg Med Chem. 2008;16(7):3800-8

12.   Zhiqiang Pan et al. Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol BMC Med Genomics. 2008;1:7.

13.   LI Z et al. Pistachio nuts reduce triglycerides and body weight by comparison to refined carbohydrate snack in obese subjects on a 12-week weight loss program J Am Coll Nutr. 2010 Jun;29(3):198-203

14.   CWV Kendell, et al. The impact of pistachio intake alone or in combination with high-carbohydrate foods on post-prandial glycemia Eu J Clin Nutr. 2011;65:696-702

15.   Michelle Wein et al. Almond Consumption and Cardiovascular Risk Factors in Adults with Prediabetes J Am Colle Nutr. 2010;29(3):189-197

16.   Lei Jia et al. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials Am J Clin Nutr. May 26, 2010

17.   Christian Heiss et al. Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease J Am Coll Cardiol, 2010; 56:218-224

18.   Davison et al. Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects 2008, Int J Obesity 32(8):1289

19.   Fisher et al. Aging and vascular response to flavanol rich cocoa 2006, J Hypertension 24:1575.

20.   Engler MB et al. Flavanoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults J Am Col Nutr 2004, 23(3):197-204

21.   Fisher et al. Flavanol-rich cocoa induces nitric oxide-dependent vasodilation in healthy humans 2003, J Hypertension 21:1

22.   Arlet Berecochea-Lopez et al. Fungal Chitin-Glucan from Aspergillus niger Efficiently Reduces Aortic Fatty Streak Accumulation in the High-Fat Fed Hamster, an Animal Model of Nutritionally Induced Atherosclerosis J. Agric. Food Chem. 2009, 57, 10931098

23.   Audrey Deschamps et al. Managing oxidative stress with a vegetal ingredient, chitin-glucan Agro FOOD. July/August 2009; 20(4):12

24.   Audrey M. Neyrinck et al. Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitinglucan fiber improves host metabolic alterations induced by high-fat diet in mice J Nutr Biochem. March 14, 2011

25.   Sally Tandy et al. Dietary Krill Oil Supplementation Reduces Hepatic Steatosis, Glycemia, and Hypercholesterolemia in High-Fat-Fed Mice J Agric Food Chem. 2009;57 (19):93399345

26.   Stine M. Ulven et al. Metabolic Effects of Krill Oil are Essentially Similar to Those of Fish Oil but at Lower Dose of EPA and DHA, in Healthy Volunteers Lipid. Nov. 2, 2010

27.   Constance Schmelzer et al. Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans IUBMB Life. 2011 Jan;63(1):42-8. DOI: 10.1002/iub.413

28.   Belcaro G. et al. Investigation of Pycnogenol® in combination with coenzymeQ10 in heart failure patients (NYHA II/III) Panminerva Medica 2010 June;52(2 Suppl 1):21-5

29.   Asia. Pacific. J. Clin. Nutr. 1997; 6(1): 72-75

30.   Am J Clin Nutr 1991; 53 (Suppl 4): 1021S-1026S

31.   J Nutr Sci Vitaminol 2006; 5(6): 473-478

32.   Kay Hay Yuen et al. Effect of Mixed-Tocotrienols in Hypercholesterolemic Subjects Fun Foods Health Dise. 2011:(3)106-117

33.   Arch Pharm Res. 2008; 31 (9); 1212-1217

34.   Robert G. Lefavi et al. Lipid-Lowering Effect Of A Dietary Chromium (Iii)- Nicotinic Acid Complex In Male Athletes Nutrition Research 1993;13:239-249

35.   Maier JA Low Magnesium and arthrosclerosis: an evidence-based link. Mol Aspects Med 2003 Feb 6;24(103):137-46

36.   Weaver K and Speigel KM, Platelet Functional Responses to Oral Doses of magnesium and Fish Oil in Human Volunteers. JACN 7, 1988:407

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