Todd Runestad, Content Director, NaturalProductsInsider.com, Sr. Supplements Editor

January 1, 2007

28 Min Read
Heart-healthy foods keep the beat

From heart bars to soy foods and functionally fortified beverages, the healthy-foods industry is taking aim at heart health. Todd Runestad looks at leading foods and food components that can be used by product developers to bring the next generation of cardio foods to market

berries.jpgCardiovascular disease is the top health condition affecting people in Western nations. Beyond the range of dietary supplements said to address one area of heart health or another, foods are beginning to make a play. A trip down cereal aisles in grocery stores, for instance, exhibits any number of cereal boxes with heart logos printed on them, containing official pronouncements from health authorities vouchsafing the product for consumer heart benefit (as part of a diet low in saturated fat and cholesterol).

Breakfast is shaping up to be a prime eating event for food formulators to take aim at consumer heart health. So cereals now contain elevated quantities of fibre, which lowers blood cholesterol levels. And they may contain soy protein — 25g/day, or 6.25g/serving, rates a health claim of reducing the risk of heart disease. Omega-3s, widely available in frozen waffles as well as cereals, boast a qualified health claim in reducing the risk of coronary heart disease; the FDA ruling recommends that consumers not exceed more than a total of 3g per day of EPA and DHA omega-3 fatty acids, with no more than 2g per day from a dietary supplement, hence paving the way for increased food integration.

Plant sterols, derived from natural vegetable oils such as corn and soy, can also lower cholesterol levels at dosage levels of 0.8g/day, in particular when incorporated into fat matrices. Not only are sterols found in cereals but their original source was in butter-style spreads, and more successfully in orange juice. Just like that, one functional ingredient is now fully integrated into the breakfast experience.

Food manufacturers have been working diligently to eliminate trans fatty acids from food products because of their manifest increased heart-disease risk, which is even worse than the saturated fats they were produced to replace.

Another new Harvard look at the Nurses' Health Study found foods with a higher glycaemic load to be strongly associated with an increased risk of coronary heart disease. What's more, when vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease.1

Meals eaten throughout the day can easily be either reformulated or fortified with functional ingredients to improve consumers' cardiovascular health profiles. The following review assesses some common, as well as up-and-coming, ingredients available for food and supplement manufacturers looking to offer condition-specific products and formulations for cardiovascular health.

Bioactive fortificants
Sterols likely lead the way in successful functional-foods integration. The road has not been easy, particularly in the US, where the spread products that proved so successful in Europe never panned out. It was not until orange juice became a delivery system of choice that sterols really caught on.

Among the foods that may qualify for health claims based on plant stanol ester content are spreads, salad dressings, snack bars and dietary supplements in softgel form. Foods that carry the claim must also meet the requirements for low saturated fat and low cholesterol, and must also contain no more than 13g of total fat per serving, and per 50g. However, spreads and salad dressings are not required to meet the limit for total fat per 50g if the food label bears a disclosure statement referring consumers to the Nutrition Facts section of the label for information about fat content. In addition, except for salad dressing and dietary supplements, the food must contain at least 10 per cent of the Reference Daily Intake (RDI) or Daily Reference Value (DRV) for vitamin A, vitamin C, iron, calcium, protein or fibre. The FDA is also requiring, consistent with other health claims to reduce the risk of coronary heart disease, that the claim state that plant sterol and plant stanol esters should be consumed as part of a diet low in saturated fat and cholesterol.

Scientific studies show that 1.3g per day of plant sterol esters or 3.4g per day of plant stanol esters in the diet are needed to show a significant cholesterol-lowering effect of about 10 per cent. In order to qualify for this health claim, a food must contain at least 0.65g plant sterol esters per serving or at least 1.7g plant stanol esters per serving. Sterols' effects are enhanced with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20 per cent.2 The claim must specify that the daily dietary intake of plant sterol esters or plant stanol esters should be consumed in two servings eaten at different times of the day with other foods.

B vitamins stand out among standard vitamins and minerals routinely fortified into foods. Vitamin B6 and folic acid at levels above the current recommended dietary allowance may be important in the primary prevention of coronary heart disease. Harvard researchers teased this bit of information out of the Nurses' Health Study of 80,000 women. Those with the highest quintile of folate intake (696mcg/day) vs lowest (158mcg/day) and highest vitamin B6 (4.6mg/day) vs lowest (1.1mg/day) had significantly reduced risk of coronary heart disease.3

Another important B vitamin, niacin, is the king of lowering cholesterol. Like many natural bioactives, it lowers LDL cholesterol. What sets niacin apart from the competition is that it also increases HDL cholesterol.4 Indeed, compared even to statin drugs, niacin comes out on top as statins are effective in only lowering LDL cholesterol. Niacin, on the other hand, is the most potent drug available for lowering plasma levels of triglycerides and raising HDL levels.5 To be sure, therapeutic doses of niacin range between 1,000 and 1,500mg/day whereas the recommended daily allowance is 14-16mg/day and food product developers are hard-pressed to put into products any more than that.

Vitamin E, in 2001, was reported to be taken by 48 per cent of cardiologists. This boosted the fortunes of the primary fat-soluble antioxidant that protects lipids from peroxidation. This was supported by the Cambridge Heart Antioxidant Study (CHAOS), published in Lancet in 1996, showing a reduction in coronary disease with vitamin E supplementation.6 By the turn of the century, 'antioxidant' was a household word. But in 2005, an infamous meta-analysis of 19 mostly negative studies concluded a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation.7 Vitamin E sales dropped by about 40 per cent at the news, according to IRI data.

So, which is it? A new view, promulgated by vitamin E expert Maret Traber, PhD, at the Linus Pauling Institute in Oregon, concluded that significant reductions in cardiovascular disease risk are observed as serum alpha-tocopherol values increase from 9.1mg/L to about 13mg/L. This high end — which correlates to the recommended daily amount of dietary vitamin E — happens to be an amount that is greater than that estimated to exist in 93 per cent of men and 96 per cent of women in the United States.8 Traber notes that normolipidaemic subjects have serum alpha-tocopherol concentrations of 8.6mg/L, which can be raised to 14.2mg/L by the daily consumption of 100IU vitamin E. This intake of vitamin E, says Traber, might be "achieved only with supplements, given the dietary habits of most Americans and the observation that vitamin E-rich food sources are less popular foods, such as nuts, seeds and vegetable oils, including olive, sunflower or safflower oils." 9

Two other aspects of vitamin E bear mentioning. One is that the vitamin E family is comprised of four mixed tocopherols and four mixed tocotrienols, even though by far the main commercial version is alpha-tocopherol. But research shows that the full spectrum of all eight forms, while more expensive, has the best vitamin E benefits overall. For example, in one study, conducted by Soft-Gel Technologies in 2003, mixed tocopherols had greater antioxidant activities than alpha-tocopherol alone. 10 And yet only alpha-tocopherol is used to fortify foods. Secondly, natural vitamin E (d-alpha-tocopherol) has roughly double the bioavailability of synthetic vitamin E (dl-alpha-tocopherol).11 Although synthetic vitamin E is less expensive than natural, it is not twice as cheap, so manufacturers looking for quality over price choose natural vitamin E.

Potassium had a profile that increased following the FDA's health claim of potassium in 2000, stating, "Diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke." Foods — actually, this probably applies more to juices than anything — must contain at least 350mg of potassium (10 percent of the daily value) and 140mg or less of sodium. In addition, qualifying foods must have less than 3g fat, 1g or less saturated fat, and 20mg or less cholesterol.

Tropicana Products, makers of citrus juices, petitioned to add this to their packaging. While orange and grapefruit juices are good sources of potassium, there are many others. Equally good sources include tomato and pineapple juices, green peas, and meats. Among the best sources of potassium are baked potatoes, bananas and cow's milk.

Although the mechanisms for potassium's effects on blood pressure and stroke risk are unknown, it has been suggested that potassium may affect vasoconstriction and vascular resistance.12

Ribose is a naturally occurring monosaccharide the body uses to stimulate the synthesis of adenosine triphosphate (ATP), an essential energy compound. ATP is critical to health and maintaining normal energy-dependent body functions. Ribose is the essential component in the making of ATP. Depleted levels of ATP are typical in heart-failure patients as ATP supports systolic and diastolic work of the heart.13 The heart's ability to resynthesise ATP is limited by the supply of D-ribose, which studies show can increase tolerance to myocardial ischaemia.14

Ribose can be taken in bars, drinks, a slightly sweet-tasting powder and tablets. Doses of 5-7g/day are seen as helpful as a preventive for cardiovascular disease. Those with existing cardiovascular disease stand to benefit at doses of 7-10g/day.

Coenzyme Q10 is concentrated in the cell's mitochondria — the power plant of the cell. It thus plays a critical role in energy creation because it aids in the generation of ATP. Also, co-Q10 happens to accumulate in the heart tissue more than any other place in the human body. Because it helps in the pumping action of the heart, it is here that co-Q10's heart-health benefits become manifest, in particular such cardiac conditions as congestive heart failure (in which the heart becomes congested with blood and is dangerously weakened) and high blood pressure.15,16 co-Q10 deficiencies are found in many people suffering from cardiovascular disease, congestive heart failure, cardiomyopathy and hypertension.17,18,19,20

Because co-Q10 is a fat-soluble nutrient, its absorption is enhanced in the presence of fats. This means that when the supplement is taken apart from meals, or with fat-free meals, its absorption and bioavailability is decreased. Manipulating nutrient delivery is already a challenge in the food industry, and co-Q10 has only recently been used by food formulators, using special water-soluble powders. The richest food sources are organ meats, beef, soy oil, sardines and sardines, and it is also found naturally in spinach, broccoli, nuts, fish and meats.

Vitamin K2 is a newly recognised vitamin that has benefits for both cardiovascular health as well as bone health. The reason for both, apparently disparate, conditions is that vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification — the so-called 'hardening of the arteries.' A low dietary Vitamin K2 (menaquinone-7) intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk.21 Conversely, a recent study with 4,700 subjects found individuals with the highest K2 consumption exhibited a 50 per cent decreased risk of myocardial infarction, 50 per cent decreased risk for cardiovascular mortality and a 25 per cent decreased all-cause mortality.22

The added appeal of vitamin K2 is that it signals a potential paradigm shift away from cholesterol, triglycerides, blood pressure, age and other common risk factors for cardiovascular disease. Vitamin K2 is about the amount of calcium in one's arteries that should be in the bones. A study in the New England Journal of Medicine states, "According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not."23 Vitamin K2 is found naturally in soy products and leafy vegetables such as brussels sprouts, broccoli, cauliflower, chard and spinach. It is also available as a supplement.

Heart-healthy foods
In many cases food developers need not dig through the scientific literature to find the precise bioactive agent within foods that plays a role in heart health. A better course could be to use the actual food source from which the components are derived, whether the bioactives be isoflavones, lycopene, flavonoids or omega-3 fatty acids.

Soy: The original heart-healthy food, soy has taken a few hits lately by organisations saying its 1999 heart-health claim was not all it was cracked up to be. An American Heart Association committee, after reviewing 22 dietary soy-protein studies and 19 of soy isoflavones, say they found no effect on LDL cholesterol or other lipid risk factors. This stands in direct contrast to a seminal 1995 review of 38 studies published in the New England Journal of Medicine concluding that soy protein consumption resulted in 13 per cent lower LDL, 10 per cent lower triglycerides and about two per cent higher HDL cholesterol.24 Indeed, research accumulated over the past decade suggests soy protein might decrease atherosclerosis and cardiovascular disease by improving lipid profiles and also through beneficial effects on blood pressure,25 vascular function,26 platelet activation and aggregation,27 LDL oxidation,28 and C-reactive protein and high iron levels.29

Of course, soy and isoflavone products remain good foods because they have a high content of polyunsaturated fats, fibre, vitamins and minerals, a complete amino acid profile, and low saturated fat content — soy's far lower saturated-fat content alone makes it a heart-healthier choice to meat products. (For more on soy-meat analogue formulation ideas, click here.)

The original health claim is available only for foods containing intact soy protein; it does not extend to isolated substances from soy protein such as the isoflavones genistein and daidzein. Foods must contain at least 6.25g/serving soy protein, as well as contain less than 3g fat; less than 1g saturated fat; less than 20mg cholesterol; and a sodium value of less than 480mg for individual foods, less than 720mg if considered a main dish and less than 960mg sodium if considered a meal.

Also of note on the soy front are soybean oils, which are rapidly being reformulated to eliminate the hydrogenation process and thus trans fatty acids. One new study assayed soybean oils with altered fatty acid profiles relative to common soybean and partially hydrogenated soybean oils.30 The experimental oils were soybean oil, low-saturated fatty acid soybean oil designed by selective breeding, high-oleic acid soybean oil developed by genetic modification, and low-alpha linolenic acid soybean oil developed by selective breeding. While all resulted in more favourable lipid and lipoprotein concentrations than did partially hydrogenated fat, the high-oleic trended better in some of the markers, such as LDL and HDL cholesterol concentrations. Trials such as this should help move the food manufacturing and supply worlds closer to developing products that are not just convenient for producers or growers but also — indeed, more importantly — house improved consumer benefit.

Along these lines, the FDA granted a heart-health claim in October 2006 for canola oil's potential to reduce the risk of coronary heart disease because of its unsaturated fat content. Canola has 93 per cent unsaturated fats and the lowest percentage saturated fat of any common edible oil.

maters.jpgTomatoes: The US FDA recently issued a grudging qualified health claim for tomatoes or tomato sauce in reducing the risk of prostate cancer. A new, double-blind, placebo-controlled, crossover study out of the UK and published in September 2006, concludes that the equivalent of two to six tomatoes can improve heart health. The tomato extracts decreased the accumulation of blood platelets, thereby reducing the risk of forming a blood clot that can lead to heart attack or stroke.31 Of note to product developers, lycopene in tomatoes is more bioavailable when the tomatoes are processed or cooked.32

Cranberries: Flavonoids are polyphenolic compounds found in a large selection of fruits and vegetables. These dietary antioxidants inhibit LDL oxidation, inhibit platelet aggregation and adhesion, and decrease total and LDL cholesterol.33Cranberries are particularly rich in these flavonoids. In 2005, Canadian researchers conducted a 14-day study on 21 men to see if about a pint of cranberry juice a day would have any effect on cardiovascular health markers. The intervention led to a decrease in plasma oxidised LDL concentrations as well as an increase in antioxidant capacity.34 Another intervention study, presented at the Canadian Cardiovascular Society's Annual Congress in Calgary in 2004, gave 30 men with elevated LDL levels a serving of Ocean Spray Light Cranberry Cocktail a day. After 12 weeks, HDL cholesterol levels rose by eight per cent.

walnuts.jpgWalnuts: One of the oldest food ingredients known to mankind, walnuts are a rich plant source of alpha-linolenic acid, a key essential fatty acid from which omega-3 fatty acids are derived. In 2004, the US FDA minted the nut with a qualified health claim for its ability to lower LDL cholesterol, a valid biomarker for coronary-hear-disease risk. The health claim is qualified because the sum of the evidence totaled only two short-term studies with small sample sizes demonstrating a positive effect of walnuts in reducing LDL cholesterol when isocalorically replacing other fat-containing foods.35,36 The FDA concluded that the evidence shows that walnuts affect serum lipids by replacing dietary saturated fat with unsaturated fat and would not comment on the potential of its omega-3 content having any bearing on the nuts' healthfulness. The lowest intake level of walnuts to show benefit is 1.5g/day.35

A study published in October 2006 found walnuts can improve artery function and may be more important in a Mediterranean-type diet than olive oil. A single walnut meal positively affected blood flow, noted researchers, who also gave additional support to the idea that the alpha-linolenic acid plays a crucial role in walnuts' heart-healthiness.37

Fish: In 2004, the FDA bequeathed a qualified health claim for reduced risk of coronary heart disease on conventional foods that contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids. Typically, EPA and DHA omega-3 fatty acids are contained in oily fish, such as salmon, lake trout, tuna and herring. These fatty acids are not essential to the diet; however, scientific evidence indicates that these fatty acids may be beneficial in reducing coronary heart disease (CHD).

Intervention studies in both the general healthy population and patients with established coronary heart disease have evaluated the effects of EPA and DHA omega-3 fatty acids on physiological endpoints (eg, LDL cholesterol, triglycerides, platelet aggregation), some of which have been proposed as possible mechanisms for the CHD risk reduction by EPA and DHA omega-3 fatty acids.38

The supplements industry has capitalized on concerns of mercury and other heavy-metal contamination of certain fish stocks. The functional foods industry, meanwhile, has been able to offer food-grade DHA and EPA for integration into the widest variety of foods. These days, it seems, whole fish is almost beside the point. [For more on omega-3 oils, see the February 2007 issue of FF&N.]

Making the best of foods
Developing foods to increase their cardiovascular profile does not have to mean a magic-bullet food — not even pharmaceuticals can boast that. But heart disease is the leading cause of preventable death in the world, and creating foods that help nudge consumers into eating healthier foods is a good start.

Regulatory agencies are also helping. The FDA, for example, in October 2006 approved a qualified health claim for canola oil and heart health when it replaces saturated fats.

Of note, different ingredients can act via different mechanisms to improve heart health. For instance, sterols and fibres have a hypocholesterolaemic effect while omega-3s lower triglycerides.39 By determining the mechanisms of action that an ingredient possesses, foods can be developed that benefit from a range of actions.

Respond: [email protected]

Another important B vitamin, niacin, is the king of lowering cholesterol

The body uses ribose to stimulate the synthesis of adenosine triphosphate

Lycopene is more bioavailable when the tomatoes are processed or cooked

Fibre finds its moment
Particularly since health authorities increased daily recommended fibre intake levels in 2002, food manufacturers have seized upon the public health message to boost fibre intake in foods such as bars and cereals as well as beverages. Dietary fibre intake among adults in the United States averages about 15 grams a day. Some organisations recommend that dietary fibre intake should be 25—30 grams a day for older children, adolescents and adults.

Dietary fibre is the term for several materials that make up the parts of plants the body cannot digest. Fibre is classified as soluble or insoluble. Soluble fibre attracts water and turns to gel during digestion. This slows digestion. When eaten regularly as part of a diet low in saturated fat and cholesterol, soluble fibre has been shown to help lower blood cholesterol by 10-15 per cent, which can help prevent heart disease.1

Oats have the highest proportion of soluble fibre of any grain. Foods high in soluble fibre include oat bran, oatmeal, beans, peas, rice bran, barley, nuts, citrus fruits, strawberries and apple pulp. Insoluble fibre is found in foods such as wheat bran, vegetables and whole grains. It appears to speed the passage of foods through the stomach and intestines and adds bulk to the stool.

High intake of dietary fibre has been linked to a lower risk of heart disease in a number of large population studies using food-frequency questionnaires.2,3,4 In these groups, which followed nearly 40,000 female health professionals and more than 43,000 male health professionals, the highest quintiles consumed between 22.9g/day and 26.3g/day whereas the lowest quintiles ranged from 11.5g/day to 12.5g/day.

Of note, among different sources of dietary fibre — cereal, vegetables, fruit — only cereal fibre, found in grains, was strongly associated with a reduced risk of coronary heart disease.

New forms of fibre and new ways food technologists have developed of working with fibre have contributed greatly to increasing fibre content in foods. White rice, bread and pasta are being replaced with brown rice and whole-grain products.

Cereal manufacturers are seeing the light that refined or processed grains strip out fibre-rich bran and germ and are choosing whole-grain cereals. International dishes, such as Indian or Middle Eastern, use whole grains and legumes as part of the main meal, as in Indian dahls, or in salads, as with tabbouleh. Instead of going whole hog with new lines of ethnic fare, manufacturers can take healthful elements of those dishes and incorporate them into traditional lines.

—TR

References
1. Shamliyan TA, et al. Are your patients with risk of CVD getting the viscous soluble fiber they need? J Fam Pract 2006 Sep;55(9):761-9.
2. Liu S, et al. A prospective study of dietary fiber intake and risk of cardiovascular disease among women. J Am Coll Cardiol 2002 Jan 2;39(1):49-56.
3. Rimm EB, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996 Feb 14;275(6):447-51.
4. Wolk A, et al. Long-term intake of dietary fiber and decreased risk of coronary heart disease among women. JAMA 1999 Jun 2;281(21):1998-2004.


Select Suppliers: ingredients for heart-healthy products

ADM: CardioAid plant sterols are GRAS for spreads, salad dressings, beverages, bars, dairy, juices, bakery and more.
www.admworld.com

Cargill: CoroWise sterols are derived from all-natural plant sources and are formulated for use in food, beverages and dietary supplements.
www.cargillhft.com

Carotech: Tocomin is a full-spectrum palm-based mixture of tocotrienols and tocopherols.
www.carotech.net

Cognis: Vegapure natural plant sterols and esterol esters and Omevital omega-3 fatty acids support heart health.
www.cognis.com

Croda: Incromega EPA and DHA come in a number of combinations for different applications.
www.crodausa.com

Davos Life Science: Providing a full spectrum of palm tocotrienols, including purified isomers and tocotrienol-enriched fractions for foods, beverages, spreads and supplements.
www.davoslife.com

Decas: PACran is the industry's first and only clinically supported proanthocyanidin (PAC) standardized cranberry powder, standardised to 1.5% PACs.
www.healthyberry.com

Dow: Fortefiber is a soluble dietary fibre made from cellulose, available in a variety of grades, nonfermentable and nonallergenic, and can be added to bars, bakery, drinks and chews.
www.fortefiber.com

Lonza: Niamax is a brand name for a sustained-release niacin tablet, supplied by world leader Lonza and used to reduce cholesterol.
www.lonza.com

Lyc-O-Red: Lyc-O-Mato lycopene powder for foods from infant formula to bakery imparts the health benefits of tomato lycopene complex without the tomato taste, sugar and acidity.
www.lycored.com

Martek: life'sDHA, as an oil or micro-encapsulated powder, maintains chemical and sensory integrity as well as shelf-life stability under many processing conditions.
www.lifesdha.com

Ocean Nutrition: Meg-3 is the world leader in micro-encapsulated fish oil, making it available for the range of foods and drinks with no taste or colour changes.
www.ocean-nutrition.com

Ocean Spray: Cranberry king provides the food industry with dried, frozen, concentrates, juice, pureés and powders for commercial applications.
www.oceansprayitg.com

Pizzey's Milling: Flaxseed ingredients provide texture and flavour for cereals, bars, beverages, supplements and more.
www.pizzeys.com

Raisio: Benecol stanol esters as solids or liquids act like fats; powders for ready-mix and pre-mix powders for yoghurts, spreads, dairy and more.
www.benecol.net

Solae: About 80 percent of all clinical research on soy protein, and many of the studies supporting the FDA-approved health claim, are based on research using Solae soy protein.
www.solae.com

Source One: Sytrinol is a patented formula derived from natural citrus and palm-fruit extracts made by KGK Synergize, distributed by Source One to lower cholesterol.
www.source-1-global.com

Valen Labs: Bioenergy and Corvalen, ribose ingredients from Bioenergy, the exclusive manufacturer, marketer and distributer of ribose-based products.
www.valenlabs.com

Wright Group: The O-3 Complete range with SuperCoat microencapsulations can be integrated into SuperBlend value-added premixes and custom-tailored.
www.thewrightgroup.net


References
1. Halton TL, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 2006 Nov 9;355(19):1991-2002.
2. Katan MB, et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003 Aug;78(8):965-78.
3. Rimm EB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998 Feb 4;279(5):359-64.
4. Morgan JM, et al. The effects of niacin on lipoprotein subclass distribution. Prev Cardiol 2004 Fall;7(4):182-7.
5. Chrysant SG, Ibrahim M. Niacin-ER/statin combination for the treatment of dyslipidemia: focus on low high-density lipoprotein cholesterol. J Clin Hypertens (Greenwich) 2006 Jul;8(7):493-501.
6. Stephens NG, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781-6.
7. Miller ER III, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37-46.
8. Maras JE, et al. Intake of alpha-tocopherol is limited among US adults. J Am Diet Assoc 2004;104:567-75.
9. Traber MG. How much vitamin E? ... Just enough! Am J Clin Nutr 2006;84:959-60.
10. Naguib Y, et al. Antioxidant activities of natural vitamin E formulations. J Nutr Sci Vitaminol (Tokyo) 2003 Aug;49(4):217-20.
11. Burton GW, et al. Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 1998 Apr;67(4):669-84.
12. Moudgil R, et al. The role of k+ channels in determining pulmonary vascular tone, oxygen sensing, cell proliferation, and apoptosis. Microcirculation 2006 Dec;13(8):615-32.
13. Taegtmeyer H, et al. Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. J Am Coll Cardiol 1985;6:864-70.
14. Pauly DF, Pepine CJ. D-ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Therapeut 2000;5(4):249-58.
15. Sander S, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Car Fail 2006 Aug;12(6):464-72.
16. Hodgson JM, Watts GF. Can coenzyme Q10 improve vascular functionand blood pressure? Potential for effective therapeutic reduction in vascular oxidative stress. Biofactors 2003;18(1-4):129-36.
17. Morisco C, et al. Effect of coenzyme Q10 in patients with congestive heart failure: a long-term multicenter randomized study. Clin Invest 1993;71:S134-6.
18. Sole MJ, Jeejeebhoy KN. Conditioned nutritional requirements: therapeutic relevance to heart failure. Herz 2002 Mar;27(2):174-8.
19. Artuch R, et al. Ubiquinone: metabolism and functions. Ubiquinone deficiency and its implication in mitochondrial encephalopathies. Treatment with ubiquinone. Rev Neurol 1999 Jul 1-15;29(1):59-63.
20. Yamagami T, et al. Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension. Res Commun Chem Pathol Pharmacol 1975 Jun;11(2):273-88.
21. Maas AH, et al. Vitamin K intake and calcifications in breast arteries. Maturitas 2006 Sep 27; [Epub ahead of print].
22. Geleijnse JM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam study. J Nutr 2004;134:3100-5.
23. Rosenhek R, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000 Aug 31;343(9):611-7.
24. Anderson JW, et al. Meta-analysis of the effects of soy protein and isolate intake on serum lipids. New Engl J Med 1995;333:276-82.
25. Crouse JR, et al. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern med 1999;159:2070-6.
26. Nestel PJ, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids I menopausal and perimenopausal women. Arterscler Thromb Vasc Biol 1997;17:3392-8.
27. Williams JK, Clarkson TB. Dietary soy isoflavones inhibit in vivo constrictor responses of coronary arteries to collagen-induced platelet activation. Coronary Artery Dis 1998;9:759-64.
28. Hanson LN, et al. Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and iron status in postmenopausal women. Am J Clin Nutr 2006;84:774-80.
29. Jenkins DJA, et al. Effect of soy protein foods on low-density lipopritein oxidation and ex vivo sex hormone receptor activity — a controlled crossover trial. Metabolism 2000;49:537-43.
30. Lichtenstein AH, et al. Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects. Am J Clin Nutr 2006;84:497-504.
31. Kennedy N, et al. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am J Clin Nutr 2006;84:561-9.
32. Holloway DE, et al. Isomerization of dietary lycopene during assimilation and transport in plasma. Free Radic Res 2000 Jan;32(1):93-102.
33. Reed J. Cranberry flavonoids, atherosclerosis and cardiovascular health. Crit Rev Food Sci Nutr 2002;42(3 Suppl):301-16.
34. Ruel G, et al. Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption. Metabolism 2005 Jul;54(7):856-61.
35. Iwamoto M, et al. Serum lipid profiles in Japanese women and men during consumption of walnuts. Eur J Clin Nutr 2002;56:629-37.
36. Sabaté J, et al. Effects of walnuts on serum lipid levels and blood pressure in normal men. New Engl J Med 1993;328:603-7.
37. Cortes B, et al. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol 2006 Oct 17;48(8):1666-71.
38. Laidlaw M, Holub BJ. Effects of supplementation with fish oil-derived n-3 fatty acids and alpha-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr 2003;77(1):37-42.
39. Castro IA, et al. Functional foods for coronary heart disease risk reduction: a meta-analysis using a multivariate approach. Am J Clin Nutr 2005 Jul;82(1):32-40.

About the Author(s)

Todd Runestad

Content Director, NaturalProductsInsider.com, Sr. Supplements Editor, Natural Products Insider

I've been writing on nutrition science news since 1997. I'm The content director for NaturalProductsInsidercom and digital magazines. Other incarnations: supplements editor for newhope.com, Delicious Living and Natural Foods Merchandiser. Former editor-in-chief of Functional Ingredients magazine and still cover raw material innovations and ingredient science.

Connect with me here https://www.linkedin.com/in/toddrunestad/

My daily vitamin regime includes a morning smoothie with a range of powders including protein, collagen and spirulina; a quality multi, B complex, C with bioflavonoids, >2,000IU vitamin D, E, magnesium, high-selenium yeast, PQQ, choline, alpha-lipoic acid with carnitine, coQ10, fish oil concentrate, probiotics and some adaptogenic herbs. 

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