Cardiovascular Wellness

Cardiovascular Wellness

by Heather Granato

Cardiovascular disease (CVD) is a primary or contributing cause to more than 1.3 million deaths in the United States each year, according to the most recent statistics from the American Heart Association (AHA). CVD has been the No. 1 killer in the United States every year since 1900, with the exception of 1918, and claims as many lives each year as the next seven leading causes of death combined. And the cost of CVD in the United States for 2002 was estimated at $329.2 billion, including health expenditures and lost productivity resulting from morbidity and mortality.

CVD is not just one disease, but a combination of conditions affecting the circulatory system. Almost 62 million Americans have one or more types of CVD, according to AHA (www.americanheart.org), including coronary heart disease (CHD, which includes myocardial infarction and angina pectoris), stroke, congestive heart failure and high blood pressure. CHD is the largest single killer of American males and females--about every 29 seconds, an American suffers a coronary event, and every minute, someone dies from one.

While CVD holds steady as the top disease in the United States, the unfortunate fact is that so many of the risk factors can be controlled. According to the Natural Marketing Institute's (NMI) Health & Wellness Trends Database--four years of trended data from more than 2,000 consumer household respondents--more than 40 percent of consumer households are managing or treating cholesterol, 27 percent are treating hypertension and 14 percent are treating heart disease. Approximately 20 percent of deaths from cardiovascular disease can be attributed to smoking. Physical inactivity is a major risk factor, comparable to that observed for smoking, high blood cholesterol and high blood pressure. And the increasing rate of obesity mirrors the climb in CVD rates.

Conversely, healthy food habits can help maintain normal blood pressure, desirable blood cholesterol levels and a healthy body weight. Research reviews have noted that prevention is the only true solution to countering CVD mortality. "Together with physical activity and healthy nutrition, more than 80 percent of all cardiovascular events can be prevented," according to researchers from the Universitatsklinikum Hamburg-Ependorf in Germany.¹ Beginning healthy habits early is important, as research from Finland showed that starting from seven months, children's dietary patterns can be modified to decrease exposure to known risk factors for coronary heart disease.² As an added benefit, the researchers noted that educating parents about healthy eating resulted in better nutritional patterns for the adults as well.

Sound nutrition includes reducing the intake of saturated fats and empty calories, and increasing fruit and vegetable consumption, as studies from the National Institutes of Health (NIH) have demonstrated an inverse association between fruit and vegetable intake and the risk of all causes of CVD.³ In November 2002, AHA also released recommendations that Americans should eat two servings of fish per week for the essential fatty acids (EFAs) that have proven beneficial in reducing the risk of CVD events. For an added benefit, many Americans are turning to nutritional compounds. Researchers from the George Washington School of Medicine in Washington, D.C., reviewed the array of compounds being used in preventing CVD.⁴ Among the herbs and supplements that were suggested for benefits and further study were garlic, hawthorn, coenzyme Q10, vitamin E, fish oil and carnitine. Other studies have indicated that sufficient intake of dietary antioxidants, whether from fruits and vegetables or red wine and tea, may help prevent atherosclerosis, a risk factor for CVD.⁵

Atherosclerosis (from the Greek athero--paste--and sclerosis--hardness) involves deposits of fats, cholesterol, cellular waste products, calcium and other substances in the inner lining of an artery. This build-up, called plaque, usually affects large and medium-sized arteries. Atherosclerosis is a major cause of cardiovascular disease.

Plaques can become unstable and rupture, causing a blood clot to form that can block blood flow in the artery. A blood clot that breaks off is called an embolus. If a clot blocks a blood vessel that feeds the heart, it causes a heart attack. If it blocks a blood vessel that feeds the brain, it causes a stroke.

Nutritionally, the goal of nutritional compounds in preventing atherosclerosis is to eliminate the cellular waste products that build up in the bloodstream. One major cause of waste is oxidation, in which free radicals damage cells, exposing them to oxygen and compromising the integrity of cell walls. To prevent this damage, nutritional compounds known as antioxidants quench the free radicals in the bloodstream by donating an electron and stabilizing the compound.

In the cardiovascular health area, two of the best-known antioxidants are vitamin C and vitamin E. According to the NMI Health & Wellness Trends Database, 38 percent of the general population is taking vitamin E daily and 35 percent uses vitamin C every day. Almost 30 percent of healthy U.S. physicians in a cohort study reported using vitamins C and E in their own diets, though there was no significant decrease in CVD mortality during the five-year follow-up.⁶ Another study, this time out of the United Kingdom, examined 20,536 adults with CHD or diabetes who were assigned to placebo or daily antioxidant supplementation (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene).⁷ Again, there was no significant reduction in five-year mortality or incidence of vascular disease, cancer or other major outcomes.

However, other studies that have combined vitamins C and E indicate these nutrients have positive effects on heart health. A double masked, two-by-two factorial study on the three-year progression of carotid atherosclerosis examined the impact of twice-daily intake of 136 IU of alpha-tocopherol, twice-daily intake of 250 mg of vitamin C, both or placebo on 520 men and women.⁸ Measurement of carotid artery mean intima-media thickness showed that atherosclerosis progression was reduced by 74 percent by supplementation with both vitamins as compared to placebo. Another double blind study on 40 patients who received a heart transplant examined whether 500 mg of vitamin C plus 400 IU of vitamin E taken twice daily reduced the risk of transplant-associated arteriosclerosis.⁹ The researchers, from Brigham and Women's Hospital in Boston, concluded supplementation retarded early progression of arteriosclerosis.

Studies and reviews of the individual vitamins have examined their ability to reduce oxidation of blood cholesterol levels and mitigate other factors contributing to CVD. A study of 102 healthy Italians age 80 and older indicated those with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth the level of those with vitamin E levels in the lowest quartile.¹⁰ Another study out of Italy looked at 310 women participating in Progetto Atena, a population-based study, and found an inverse association between preclinical atherosclerosis and the intake amount and plasma concentration of vitamin E.¹¹

A possible mechanism of action is vitamin E's ability to prevent lipid peroxidation. Finnish researchers examined the long-term effects of vitamins C and E on plasma F2-isoprostanes, a marker of lipid peroxidation, in 100 men.¹² Researchers reported that 200 mg/d of d-alpha-tocopheryl acetate lowered the plasma F2-isoprosatne concentration by 17.3 percent compared to placebo; vitamin C had no significant effect on the marker compound. Another study compared intake of 400 IU/d of dl-alpha-tocopherol to placebo for three years, and found that supplementation reduced oxidation of LDL (low-density lipoprotein) cholesterol; however, it did not reduce the incidence of atherosclerosis progression.¹³

These mixed results have raised questions in the nutrition field. A review from Tufts University in Boston noted that clinical trials on vitamin E have shown decreased lipid oxidation but no decrease in CVD, leading reviewers to suggest re-evaluating study approaches.¹⁴ Another review concurred that while vitamin E improves vasodilation and increases resistance to LDL oxidation, studies have not consistently shown protective benefits against coronary events and stroke.¹⁵

Part of the reason behind this variation, according to some researchers, is that many studies have used a single isomer of vitamin E, rather than a mixture of the four tocotrienols and four tocopherols that are naturally occurring in the fat-soluble vitamin. Researchers from the University of Hawaii at Manoa noted that mixed tocotrienols may be a more effective antioxidant than alpha-tocopherol and have the ability to reduce cholesterol levels, as well as apolipoprotein B and lipoprotein(a) plasma levels.¹⁶ And researchers from the University of Uppsala, Sweden, found that both alpha-tocopherol and gamma-tocopherol impacted the parameters of oxidation and thrombogenesis, but that gamma-tocopherol was significantly more potent than alpha-tocopherol.¹⁷ Tocotrienols can be naturally extracted from both rice and palm sources.

Studies of vitamin C have shown more consistently positive results on various CVD conditions and contributing parameters. Low levels of plasma vitamin C, for example, may be linked to an increased risk of stroke. Researchers from the University of Kuopio, Finland, conducted a 10-year, population-based study of 2,419 men with no history of stroke and found that those with the lowest levels of plasma vitamin C had a 2.4-fold increased risk of stroke compared with men with the highest levels, even after adjustment for such factors as age, smoking, diabetes and prevalent CHD.¹⁸ Also, hypertensive men with the lowest vitamin C levels had a 2.6-fold risk increase, and overweight men with low plasma vitamin C had a 2.7-fold increased risk for stroke. Similar findings were reported by researchers from Tokyo Medical and Dental University, who examined a cohort of 880 men and 1,241 women for 20 years.¹⁹ They concluded that serum vitamin C was inversely related to incidence of stroke, and the relationship was significant for both cerebral infarction and hemorrhagic stroke.

Vitamin C may specifically prevent lipid peroxidation. An in vitro study from the Linus Pauling Institute at Oregon State University, Corvallis, reviewed how vitamin C might prevent LDL modification.²⁰ They found that 200 microM of ascorbate protected neutrophil-mediated LDL oxidation for up to 15 minutes of incubation, leading the researchers to conclude that vitamin C delays oxidation by scavenging outside oxidants rather than attenuating oxidant production. An in vitro study from the Nagoya City University Medical School in Japan showed similar results, reporting that ascorbic acid inhibited peroxidative modification of copper-catalyzed LDL cholesterol.²¹

In addition to acting on blood lipids, vitamin C may also work on homocysteine, an amino acid in the blood; increased blood levels of homocysteine are related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. A study from the Institute of Preventive and Clinical Medicine in Bratislava, Slovakia, examined plasma homocysteine and vitamin C concentrations in 265 adults.²² Researchers found that homocysteine levels were significantly lower in adults with optimal (>50 mM/l) and suboptimal (23-50 mM/l) levels compared to those at a deficient (<11.5 mM/l) level.

In addition, these researchers found an inverse relationship between homocysteine levels and levels of some B vitamins--including folic acid, B6 and B12. A review from the Massachusetts General Hospital in Boston noted that Americans at risk of CVD should consume foods rich in B vitamins and supplement with folic acid (400 mg/d to 1 g/d), B12 (400 mcg/d to 600 mcg/d) and B6 (2 mg/d to 10 mg/d).²³ Clinical work out of Switzerland resulted in similar recommendations, with researchers noting that in their double blind, placebo-controlled trial of 553 patients, those who received 1 mg/d of folic acid, 400 mcg/d of vitamin B12 and 10 mg/d of vitamin B6 had significantly lower risk of adverse events such as nonfatal myocardial infarction and death.²⁴

Specific work with folate has also found that the vitamin can improve arterial function by reducing homocysteine levels. Researchers at Karl-Franzens University School of Medicine in Austria of 27 male patients with established coronary artery disease reviewed the effect of 5 mg/d of folic acid for six weeks.²⁵ They found a significant increase in plasma folate and improved vessel reactivity, suggesting that homocysteine lowering may have specific vasoprotective effects. This is supported by work out of the Chinese University of Hong Kong, in which 29 adults with hyperhomocysteinemia received 10 mg/d of folic acid for one year; treatment reduced homocysteine levels and improved endothelial function.²⁶

Another B vitamin with cardiovascular implications is niacin. A review from the University of California, Irvine, noted that niacin may be effective in increasing HDL (high-density lipoprotein) cholesterol and lowering LDL and triglycerides through a different mechanism than cholesterol-lowering drugs; therefore, combination use might work synergistically to reduce cholesterol levels.²⁷ It may work by promoting production of HDL particles with only apolipoprotein (apo) A-I, which is more effective in removing cholesterol and more anti-atherogenic.²⁸ In patients with low HDL levels, niacin treatment also appears to elevate HDL and contribute to vasorelaxation.²⁹

Pantethine, also known as vitamin B5, has also been studied for its ability to treat hyperlipidemia. A derivative of pantothenic acid, pantethine is converted to coenzyme A in the body. It has been reported to be effective at improving abnormal lipid profiles in both adults and children. It reportedly lowers elevated triglycerides and LDL cholesterol while raising levels of beneficial HDL cholesterol, and is used for treatment of hyperlipidemia as a pharmaceutical in Japan, primarily by Daiichi Pharmaceutical (which sells its Pantesin pantethine through Vernon Hills, Ill.-based Daiichi Fine Chemicals). A recent review noted that pantethine's efficacy as a hypolipidemic agent may be attributed to its ability to inhibit liver acetyl-CoA carboxylase, offering possible opportunities in treatment of obesity.³⁰

Minerals also contribute to cardiovascular wellness. High blood pressure is associated with higher sodium, alcohol and protein intakes; it is inversely related to potassium, calcium and magnesium intakes. A review of nutritional factors influencing blood pressure noted that while calcium and magnesium may not be a first-line defense against high blood pressure, the combination of nutrients in the diet is important to achieve blood pressure reduction.³¹ Magnesium, specifically, has been studied for its role in CVD; researchers from the University of Kalyani, India, noted that deficiencies of magnesium are linked to congestive heart failure, atherosclerosis, cardiac arrhythmias and more.³² Rat studies have shown the ability of magnesium to prevent the development of hypertension³³ and to serve as an antithrombotic agent that prolongs plasma clotting time.³⁴

Selenium is another mineral that plays a role in cardiovascular health. It has been particularly linked to immune function, and in a study of rats fed a high-fat diet, was shown to prevent nitric oxide production that can lead to atherogenesis.³⁵ A similar in vitro study found that selenium-supplemented cells had less expression of the inducible isoform of nitric oxide synthase, leading researchers to conclude selenium may help treat the inflammation associated with atherogenesis.³⁶ Another animal study highlighted the role of apoptosis in atherosclerosis development and the ability of selenium to serve as an antioxidant and inhibit that process.³⁷

Specialty Ingredients

Beyond vitamins and minerals, there are many nutritional compounds that can contribute to the prevention of CVD. CoQ10 (coenzyme Q10), also known as ubiquinone, is a powerful group of lipid-soluble compounds. CoQ10 is found in the highest concentrations in the heart, where it helps the cellular mitochondria metabolize fats for energy, and it helps maintain the flexibility of cell membranes. According to NMI data, 4.4 percent of consumers are using CoQ10 daily, though the percent increases to almost 6 percent in those over age 56. A review of studies on CoQ10, conducted at Oy Jurilab Ltd. in Finland, found that CoQ10 may decrease lipid peroxidation in both cell membranes and serum LDL, and thus may offer protection from the oxidative damage.³⁸

In one randomized, single blind, controlled trial on rabbits, for example, administering 3 mg/kg/d of CoQ10 after feeding a diet rich in trans-fatty acids decreased oxidative damage independent of lipid lowering.³⁹ Plaque sizes and frequencies, and cholesterol and triglyceride levels were lower and vitamin E was higher in the treatment group compared to placebo. A study of mice found that plasma from those given a high-fat diet plus 0.2-percent vitamin E and 0.5-percent CoQ10 for 24 weeks was more resistant to lipid peroxidation.⁴⁰ The supplementation also significantly decreased atherosclerosis. Similar findings were reported by researchers from the Heart Research Institute in Australia, who found that mice given a high-fat diet plus 1-percent (w/w) CoQ10 had significantly decreased lesion size and increased plasma resistance to lipid peroxidation.⁴¹

CoQ10 has also been studied in correlation with L-carnitine. A double blind study at the University of Toronto examined whether supplementation with CoQ10, carnitine and taurine (as MyoVive from Zoetermeer, The Netherlands-based Royal Numico) would improve left ventricular function in patients who underwent bypass surgery.⁴² They found that supplementation resulted in higher myocardial levels of the nutrients and improved left ventricular function. A review of clinical studies noted that metabolic deficiencies of L-carnitine and CoQ10 have been found in patients with CVD, and that supplementation may be important to patients suffering from congestive heart failure.⁴³

Carnitine's importance in CVD comes from its role in facilitating the production of energy from fat, since 70 percent of the heart's energy is derived from fat. It can also serve to remove toxic metabolites during ischemia, making the nutrient useful in treating many cardiac diseases. According to a review out of Temple University Medical Center in Philadelphia, carnitine may have beneficial effects in treating congestive heart failure, arrhythmia, peripheral vascular disease and acute ischemia.⁴⁴

Researchers using an animal model of heart failure showed that carnitine could reduce apoptosis in skeletal muscle cells and reduce levels of tumor necrosis factor alpha.⁴⁵ In a study comparing human myocardial tissue taken from 25 patients with end-stage congestive heart failure with tissue from 21 healthy donor hearts, concentrations of carnitines were significantly lower in heart-failure patients.⁴⁶ Another human study showed that supplementation with 2 g/d of L-carnitine in patients with moderate to severe heart failure significantly increased patient survival.⁴⁷

Part of carnitine's ability to protect heart tissue may also be attributed to its ability to reduce lipid peroxidation. A study from the University of Madras, India, found that 300 mg/kg/d of L-carnitine in rats caused a significant reduction in tissue lipid peroxidation and marked improvement of antioxidant status.⁴⁸ In another study, researchers induced hypercholesterolemia in rabbits; daily administration of L-carnitine (250 mg/kg) completely prevented the progression of atherosclerotic lesions, leading the researchers from the National Cancer Institute of Cairo, Egypt, to conclude that carnitine deficiency is an additional risk factor for atherogenesis.⁴⁹

Even as carnitine works to help the heart convert fat to energy, individuals can aid the process by making sure the body is getting the right type of fat. Essential fatty acids (EFAs), particularly from fish oil, have been studied for their ability to protect against cardiac death, high blood pressure and platelet aggregation. As mentioned earlier, recommendations published in the November 2002 issue of Circulation suggested that all Americans consume fish at least two times per week; it also noted that patients with existing CVD or high triglycerides consider taking between 1 g/d to 4 g/d of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) from fish oil supplements.⁵⁰ "Omega-3 fatty acids have been shown to reduce the incidence of CVD," the authors wrote. "Large-scale epidemiological studies suggest that individuals at risk for CHD benefit from the consumption of plant- and marine-based omega-3 fatty acids. Evidence suggests that EPA plus DHA supplementation ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality."

Among these studies is the GISSI-Prevenzione trial in Italy, which studied 11,323 patients receiving omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) from fish oil, vitamin E, both or neither. Study results reported in the Lancet noted that supplementation with LCPUFAs significantly reduced total mortality and myocardial infarction.⁵¹ Similar results were reported in the Physicians Health Study, which followed apparently healthy men for up to 17 years.⁵² Researchers from Brigham and Women's Hospital in Boston found that baseline blood levels of LCPUFAs were inversely related to the risk of sudden death. In the complementary Nurses Health Study out of the Harvard School of Public Health, researchers concluded that higher consumption of fish and omega-3 fatty acids was also inversely related to CHD and cardiac mortality.⁵³

Plant fats have also shown positive effects on cardiac risk factors. The National Cholesterol Education Panel recommends using plant sterols in combination with traditional, non-pharmaceutical therapies--such as limiting saturated fat and cholesterol intake, maintaining healthy body weight and doing regular exercise--to reduce LDL cholesterol levels. Researchers from Tufts University reported that recent data suggests 1.6 g/d of plant sterols can lower LDL cholesterol by 10 percent, with few side effects other than decreased levels of circulating carotenoids.⁵⁴

Results from animal studies elucidated possible methods of action. A study from Brandeis University in Neuenegg, Switzerland, reviewed the ability of phytosterols to block absorption of cholesterol, and found free phytosterols and esterfied sterols and stanols were effective in lowering plasma and liver cholesterol and blocking cholesterol absorption.⁵⁵ Other animal studies have shown the ability of phytosterols to protect against vascular and renal damage⁵⁶ and to protect against the hyperproliferation of vascular smooth muscle cells that is found in atherosclerosis.⁵⁷

However, it is not just the fats from plants that are beneficial in the realm of cardiovascular health. Polyphenols, carotenoids and other flavones from many plant sources have been studied for their abilities to prevent lipid peroxidation, inhibit the development of atherosclerosis and lower blood pressure. These plant antioxidants even help during digestion, inhibiting some of the oxidation of fats in gastric fluid.⁵⁸

One of the best-known sources of flavones is grapeseed extract. A research review from the University of Wisconsin Medical School, Madison, noted that the flavonoids in grape products may improve endothelial function and offer increased protection against LDL oxidation.⁵⁹ Another study reported in the Journal of Medicinal Food investigated a commercial grapeseed extract (MegaNatural Gold from Madera, Calif.-based Polyphenolics) along with grapes, grape juice, red wine and other grapeseed extracts, and found high plasma antioxidant activity in subjects taking 600 mg of the commercial grapeseed extract.⁶⁰ Subjects with high cholesterol also noted a change in plasma total, LDL and HDL cholesterol concentrations. Another study, presented at the American Chemical Society National Meeting in March 2000, showed that grapeseed extract (as MegaNatural Gold) showed great antioxidant capacity, as well as synergism with vitamins C and E.⁶¹

Grapeseed extract may also work well in combination with other nutritional therapies. A pilot study at Georgetown Medical Center in Washington, D.C., reviewed the ability of grapeseed extract (as ActiVin from Calif.-based San Joaquin Valley Concentrates) plus niacin-bound chromium (as ChromeMate from Benicia, Calif.-based InterHealth Nutraceuticals) to reduce cholesterol levels.⁶² Researchers gave 40 hypercholesterolemic subjects a daily dose of 200 mcg of chromium, 100 mg of grapeseed extract, chromium plus grapeseed extract, or a placebo for two months. They found that the combination of chromium and grapeseed extract significantly decreased both total cholesterol and LDL levels.

The antioxidant ability of grapeseed extract may be responsible for its ability to protect against LDL oxidation. Resveratrol, a polyphenol found in grapeseed extract, has been shown to inhibit LDL apoprotein modifications induced by oxidants in vitro.⁶³ In vivo studies have also shown the ability of red wine flavonoids to enrich plasma LDL with antioxidants, decreasing basal LDL oxidation and reducing lesion size.⁶⁴ Red wine polyphenols have also been shown to regulate endothelial nitric oxide synthase (eNOS) expression and synthesis; increased active eNOS levels may prevent development of atherosclerosis.⁶⁵

Other beverage bases also show protective abilities. Tea supplies flavones that may protect against cardiovascular disease. A population-based study of 4,807 subjects over 5.6 years found an inverse association between tea consumption and incidental myocardial infarction.⁶⁶ A meta-analysis of studies on tea consumption and CVD risk found that most studies suggested a decrease in the rate of CVD outcomes with increasing tea consumption.⁶⁷ Much stronger inverse relationships were reported from continental Europe than from other areas; combining myocardial infarction and CHD as one outcome measure, three European studies found drinking three additional cups of tea per day reduced risk by 66 percent. Green tea consumption in Japan has also shown to be protective against coronary artery disease (CAD); a study of 512 Japanese patients found an inverse relationship between green tea consumption and CAD in men, though not in women.⁶⁸

Studies on pine bark extract have shown its ability to impact several areas of cardiovascular wellness. A review from the Westfalische Wilhelms-Universitat Munster in Germany showed that Pycnogenol (available from Hillside, N.J.-based Natural Health Science) standardized French maritime pine bark extract delivers procyanidins and phenolic acids.⁶⁹ The researchers noted that Pycnogenol protects against oxidative stress, has demonstrated anti-inflammatory activity, inhibits the angiotensin-converting enzyme associated with hypertension and may treat chronic venous insufficiency. One human study suggested that the bioflavonoids in pine bark extract (as Pycnogenol) may reduce platelet aggregation in smokers, a high-risk group for CVD.⁷⁰ Another clinical study found that individuals with mild hypertension who were not taking prescribed medications had a significantly reduced systolic blood pressure in response to taking 200 mg/d of pine bark extract (as Pycnogenol).⁷¹ In addition to lowering blood pressure, pine bark extract may have favorable effects on lipid profile. A clinical study in healthy subjects found that 150 mg/d of Pycnogenol significantly increased plasma antioxidant capacity, reduced LDL levels and increased HDL levels.⁷²

Various types of carotenoids may also prevent CVD. One human study on 28 subjects with an acute ischemic stroke found that the majority of plasma carotenoids are lowered immediately after such an attack, possibly as a result of oxidative stress.⁷³ Specifically, lutein plasma changes were associated with a poor early outcome. In a three-pronged study out of the University of Southern California, researchers investigated the impact of lutein supplementation on atherosclerosis.⁷⁴ They found that progression of coronary artery thickness was related to plasma lutein among 480 human subjects; that coronary artery thickness progression declined as mice increased plasma lutein levels; and that pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner.

A great deal of research has been conducted on lycopene and CHD. A study out of Finland examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in 725 middle-aged men.⁷⁵ Researchers found that men in the lowest quartile of serum lycopene levels had a 3.3-fold increase in the risk of CHD or stroke. A second arm of the study reviewed intima-media thickness (IMT) of the common carotid artery wall in 520 men and women; low plasma levels of lycopene were associated with an 18-percent increase of IMT in men, though not in women. These findings were echoed in other human trials reviewing IMT and lycopene levels; a study from the University of Pisa in Italy on 22 patients also reported an inverse relationship between IMT and lycopene levels.⁷⁶

A review out of the University of Toronto reported that the role of lycopene in prevention of CHD is strongly suggestive, and other mechanisms besides its antioxidant capacity may contribute to this ability.⁷⁷ Among the suggested mechanisms were its abilities to inhibit the activity of an essential enzyme involved in cholesterol synthesis, altered endothelial functions and enhanced LDL degradation. Additional studies have shown that in addition to lycopene, polyphenols and other components of tomato products may be important in conferring antioxidant effects; whole tomato extract products rather than isolated lycopene might deliver these additional nutritional components.⁷⁸ Lycopene may also work in combination with other heart-healthy nutrients such as vitamin E, garlic or rosmarinic acid to inhibit LDL oxidation.⁷⁹ Researchers from Rambam Medical Center, Haifa, Israel, investigated lycopene's ability to work with other antioxidants, and found a superior antiatherogenic effect with the combination of antioxidants rather than just individual ones.

Another heart-healthy plant is soy. It has been recognized as so healthy that in 1999 the Food and Drug Administration (FDA) allowed a cardiovascular health claim to be linked to intake of 25 g/d of soy protein. In particular, soy protein has been shown to reduce levels of cholesterol and blood lipids. A study from Ulleval Hospital in Oslo, Norway, evaluated the effect of two doses of soy protein on lipid levels in 130 men and women with high LDL cholesterol levels.⁸⁰ Researchers found that adding 30 g/d to 50 g/d of soy protein to a lipid-lowering diet significantly reduced LDL cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations were also lowered. Another human study examined the cholesterol-lowering abilities of soy- and linseed-enriched foods.⁸¹ In a review of 18 subjects, plasma total, LDL and non-HDL cholesterol concentrations fell significantly, and were associated with increases in urinary isoflavone excretion.

FDA's health claim does not specify the inclusion of isoflavones, and there is some question about the benefit of isoflavones in soy protein. One study had 42 subjects consume a diet of animal protein or soy protein, each with isoflavones.⁸² Regular intake of 50 g/d of soy protein had a modest effect on blood cholesterol levels; however, there was no significant effect of isoflavones on plasma lipid levels in either the soy or animal protein diet. A research review from the Wake Forest University School of Medicine, Winston-Salem, N.C., noted there is no definite experimental evidence that the cardiovascular benefits of soy protein can be attributed to its isoflavone component.⁸³

However, research on soy protein with and without isoflavones has demonstrated that alcohol-washed protein free of isoflavones is not as effective as complete soy protein that retains its isoflavone content.⁸⁴ Dietary isoflavone intake was also found to be an important component in a review of 403 women with natural menopause.⁸⁵ Researchers from University Medical Center, Utrecht, The Netherlands, calculated isoflavone and lignan intake from a food-frequency questionnaire and found increased dietary isoflavone intake was associated with decreased aortic stiffness, with results most pronounced in older women.

Botanicals/Herbals

Many medicinal plants have been investigated for beneficial cardiovascular effects. Garlic has been reported to impact several risk factors. It normalizes plasma lipids, lowers cholesterol, inhibits platelet aggregation and reduces blood pressure.⁸⁶ A study published in the Archives of Internal Medicine reviewed 45 randomized trials and 73 additional studies on the cardiovascular-related effects of garlic.⁸⁷ Researchers, from the Audie L. Murphy Memorial Veterans Hospital in San Antonio, Texas, concluded that there may be short-term benefits of garlic on some lipid and antiplatelet factors, such as total cholesterol reduction and significant reductions in platelet aggregation. However, there were mixed effects on blood pressure outcomes and, overall, conclusions in the studies reviewed were limited by the short duration and "inadequate definition of active constituents" in study preparations. Another meta-analysis found that garlic was superior to placebo in 13 trials examining reduction in total cholesterol levels.⁸⁸ Compared to regular garlic, European wild garlic (Allium ursinum or bear's garlic) may have even more therapeutic effects; in a study at Georgetown University, rats fed 1-percent w/w wild garlic had significantly greater reductions in total cholesterol and increases in HDL.⁸⁹

Some studies have focused on the specific antioxidant functions of garlic. Researchers from Ankara University Medical Faculty in Turkey fed rabbits a cholesterol-supplemented diet, and then a normal diet plus garlic extract (1.5 ml/kg/d).⁹⁰ They found that garlic significantly improved antioxidant status and decreased both aortic peroxidation and total atherosclerotic plaque. Another study used aged garlic extract (5 mL/d of Kyolic from Mission Viejo, Calif.-based Wakunaga of America) for 13 weeks in humans with normal cholesterol levels.⁹¹ Aged garlic extract significantly inhibited both the total percentage and initial rate of platelet aggregation. A review article on aged garlic extract further suggested that it is the ability of the extract to protect against oxidative damage that is at the heart of its cardioprotective qualities.⁹²

Another beneficial botanical is hawthorn, one of the oldest recorded traditional medicines, first reported by the Greek herbalist Dioscoridies and used by Roman physicians as a heart drug in the first century A.D. Standardized hawthorn is currently used extensively by physicians in Europe for heart failure and various other cardiovascular and circulatory conditions, including angina and irregular heartbeat. One recent study out of the University of Reading, England, also found that in mildly hypertensive subjects, hawthorn reduced anxiety and diastolic blood pressure.⁹³

Licorice, used medicinally and as a flavoring since 500 B.C., also has impact on blood pressure and blood lipids. A 60-day study of 12 patients with hypercholesterolemia found that licorice root extract reduced total blood cholesterol by 5 percent, primarily attributed to a 9-percent decline in LDL cholesterol.⁹⁴ The researchers also found that blood triglyceride levels declined by 14 percent and systolic blood pressure declined by 10 percent. It is suggested that individuals with cardiac conditions use licorice only under the supervision of a medical professional.

Another ancient healing product is guggul (Commiphora mukul), an extract of a resin from the guggul tree that was used by Ayurvedic physicians in India to manage blood lipids. Studies report that guggul lowers levels of cholesterol, triglycerides and LDL cholesterol, and increases levels of HDL cholesterol. In the United States, Piscataway, N.J.-based Sabinsa Corp. holds U.S. patent No. 6,436,991 covering its guggul extract (Gugulipid) for the prevention and treatment of cardiovascular disease.

Ancient China also contributes to the pharmacological chest of CVD fighters. Apocynum venetum L., known as Asian dogbane, has been traditionally used in China and Japan as a cardiotonic and anti-hypertensive agent. A clinical study conducted in China used Apocynum venetum leaf extract in 60 subjects.⁹⁵ The mean blood pressure in 60 subjects dropped from 171 to 154 and 148 mmHg after treatment with Apocynum venetum leaf extract for four and eight weeks, respectively. Another unpublished study showed the extract's ability to increase HDL in 40 hyperlipidemic subjects. A commercially available extract (as Venetron, now available from Los Angeles-based Optipure) has also been studied for its anti-depressive qualities.

While cardiovascular disease remains the top killer of Americans, the research underlying nutritional compounds that can support heart health is expanding. It is important that consumers understand that physical activity, healthy lifestyle choices and balanced nutrition are the cornerstone to long-term cardiovascular wellness, which can then be supported with an increasing array of antioxidants, vitamins, minerals, botanicals and other nutrients.

Treatment of Heart-Related Conditions in the General Population
Source: The Health & Wellness Trends Database
The Natural Marketing Institute, 2002

Daily Usage of Supplements Among GP and Aging Consumers
Source: The Health & Wellness Trends Database
The Natural Marketing Institute, 2002

Editor's notes: Some information for this story provided by Intramedicine (www.intramedicine.com).

For a full list of references to this story, click here.