Introduction

Cardiovascular disease (CVD) represents one of the most prevalent causes of morbidity and mortality in the U.S. population today. CVD is expected to be the leading cause of death in the western world in the next 15 years secondary to the increasing prevalence of diabetes and obesity.¹ Currently, CVD accounts for approximately 38 percent of all deaths in North America. Our understanding of the processes which contribute to the development of CVD has improved significantly. As a result, much of the research in this field has focused on four aspects of this disease process: prevention of endothelial cell (blood vessel wall) dysfunction and inflammation, medical and dietary treatment of abnormal lipid profiles, treatment and control of hypertension, and the recognition and treatment of hypercoagulable (increased blood clotting) disorders. In the study of these areas, many active compounds, or phytonutrients, found in everyday foods have been shown to have significant effects toward the modulation of CVD. This review is intended to serve as a summary of the current evidence regarding the effect of certain classes of phytonutrients on the development of CVD.

Key active ingredients: Alfalfa, Barley grass, Chlorella, Spirulina

Diets rich in whole grains have been reported to result in lower rates of CVD.² Several studies have shown that these compounds possess properties associated with improved lipid profiles, reduced blood pressure, and improved blood vessel dysfunction. The treatment of cholesterol-fed rabbits with 1-4% alfalfa extracts in their diet resulted in a significant reduction in blood cholesterol levels relative to cholesterol-fed rabbits without alfalfa supplementation.³ Behall et al. from Maryland showed that total cholesterol was lowered in human subjects with mild hypercholesterolemia (200-240mg/dL) treated with 3-6g Beta-glucan per day from barley grass over a 5 week period. This barley grass extract also significantly lowered LDL levels in these same subjects. ⁴

Key active ingredients: Carrot, Spinach, Broccoli,
Tomato, Beet

Vegetables and vegetable extracts in the diet have long been thought to possess potent effects toward the prevention of CVD. These products contain carotenoids and lycopene with potent antioxidant properties which has resulted in several research studies regarding their specific effect in the cardiovascular system. Bub et al. from the Netherlands studied the effects of 6-8 weeks of carrot, spinach, and tomato supplementation on the lipoprotein carotenoid concentration and LDL oxidation in 23 healthy men. They concluded that overall carotenoid supplementation resulted in higher lipoprotein carotenoid concentrations while tomato juice resulted in a significant reduction in plasma LDL oxidation.⁷

A study by the department of neurosurgery from the University of South Florida studied the anti-oxidant effects of spinach, blueberry, and spirulina on damage to the brain after stroke. They determined that 4 weeks of supplementation resulted in a significant decrease in ischemia (stroke)-induced brain cell death.⁸

In a large, multi-center, case-control study covering ten European countries examining the correlation of anti-oxidant status and acute myocardial infarction (heart attack), elevated levels of lycopene from tomatoes was found to be protective.⁹

A group from Canada studied the effects of 14 weeks of 200mg/day broccoli supplementation on the cardiovascular status of hypercholesterolemic, stroke-prone rats. This group found that broccoli supplementation resulted in a decrease in both inflammation and oxidative stress in cardiovascular tissues, as well as average blood pressure as compared to controls.¹⁰ A group from North Carolina has reported that red wine contains high levels of betaine, an extract from beet sugar, that has been hypothesized to contribute to the anti-oxidant and cardioprotective effects of the red wine itself.¹¹

Key active ingredients: Apple, Cherry, Cranberry, Grapeseed, Green tea extract, Quercetin

The anti-oxidant properties of plant extracts such as phenolic, flavonoids, and carotenoids have been shown to possess the ability to attenuate the causes and sequelae of CVD. The Women's Health Study studied the effects of flavonoids on CVD and included approximately 40,000 subjects with a 6.9 year follow-up. They concluded that the women ingesting the highest levels of flavonoids had a 35% reduction in the risk of cardiovascular events (stroke, heart attack) and those ingesting apples had a 13-22% reduction in CVD risk factors.¹² Furthermore, Aprikian et al. found that when cholesterol fed rats were supplemented with lyophilized apples, there was a significant drop in plasma cholesterol and liver cholesterols with an increase in HDL.¹³

A group from France studied the effects of sour cherry seed extracts on the effects of retinal ischemia, a common sequela of stroke. They reported that the two week supplementation of sour cherry seeds in the diet of rats resulted in a decrease in certain inflammatory proteins after retinal ischemia compared to controls.¹⁴

The effects of cranberries and their extracts on plasma lipid profiles were studied in 21 men who were given 7ml/kg of cranberry juice for a 14-day period. This short-term dietary change was associated with a significant increase in plasma antioxidant capacity and reduction in circulating oxidized-LDL concentrations.¹⁵ The effect of a single, high-level, non-toxic dose of the grapeseed extract, procyanidin, on the lipid profiles of rats was studied. This group from Spain determined that this single dose delivery resulted in a significant decrease in levels of plasma triglycerides, free fatty acids, apolipoprotein B(apoB), and LDL-cholesterol with a slight increase in HDL-cholesterol.¹⁶

Green tea extract and, more specifically, its most active compound epigallocatechin-3-gallate (EGCG) have been shown in both animal and human studies to effect the development and incidence of CVD. Sano et al. from Japan conducted a human trial of 203 subjects to examine the relationship of green tea intake with CVD. They determined that the incidence of coronary artery disease decreased as the amount of green tea consumed per day increased.¹⁷ When EGCG was administered to rats after inducing a heart attack, this treatment resulted in a significant decrease in specific inflammatory pathways including NF-?B and AP-1.¹⁸

A trial of the flavonoid quercetin was done in human subjects by administering either 150 of 300mg daily. This study showed that quercetin is bioavailable in oral form and succeeds in significantly decreasing platelet aggregation, a key component of blood clot formation.¹⁹

Key active ingredients: Flaxseed meal, Guar Gum, Glucomannan

In recent studies, dietary fiber and their corresponding phytoestrogens have been suggested to play a role in the treatment of hypercholesterolemia. In a double-blinded, randomized study of the effects of flaxseed supplementation on the lipid profiles of 58 post-menopausal women conducted at the University of Oklahoma, researchers found that 40g daily of flaxseed over 3 months resulted in a reduction of total cholesterol and non-HDL-cholesterol by 6% with relative reductions in triglyceride levels of 12.8%.²⁰

When glucomannan was given to cholesterol-fed rats, those treated with the glucomannan supplement showed significantly lower cholesterol levels, higher HDL levels, and lower lipid peroxidation levels relative to those not treated with glucomannan.²¹

In a rat model, researchers from France have shown that the addition of guar gum to a regular diet resulted in a decrease in total cholesterol as a result of altered intestinal bile acid reabsorption.²²

Key active ingredients: Resveratrol, Ginkgo biloba, Curcumin, Bilberry, Ginger

Many of the known polyphenols, ginkgolides, curcuminoids, and anthocyanins have been found to promote vascular health in a multitude of ways. Resveratrol, a polyphenolic compound found in red wine, was found to upregulate the nitric oxide pathway in rats, potentially providing a cardio-protective effect while also preserving endothelium-dependent relaxation in arterial samples from humans undergoing coronary-artery bypass grafting.^{23, 24}

Treatment of human aortic endothelial cells with ginkgo biloba extract at 50µg/ml for 18 hours resulted in a decrease in TNF-alpha induced inflammation and endothelial adhesiveness as measured by intracellular reactive oxygen species formation, NF-kappaB and AP-1 activation, and adhesion molecule expression.²⁵

Homocysteinemia, high levels of a protein present in human serum as a common part of biochemical pathways, has been shown in many studies to create a increased tendency for blood to coagulate. As a result, physicians now recognize homocysteinemia as an independent risk factor for the development of CVD similar to diet, smoking, and activity levels. Ramaswami et al. from the Baylor School of Medicine has shown that the homocysteine-induced superoxide-anion production and eNOS downregulation, which contributes to endothelial dysfunction and impaired healing in the vessel wall, is significantly blocked by curcumin treatment.²⁶ They suggested that dietary curcumin, along with proper vitamin supplementation, play a key role in the treatment of patients with hyperhomocysteinemia.

The treatment of porcine coronary arteries with the anthocyanin extract bilberry has been shown to preserve endothelium-dependent relaxation while protecting the arteries from reactive-oxygen species.²⁷

A group from Australia showed that gingerols, the active compound in ginger, are effective in inhibiting platelet activation in similar fashion to aspirin. They noted that the effect of gingerols was approximately half of that of aspirin and likely functioned similarly by inhibiting COX enzyme activity.²⁸

With cardiovascular disease increasing in prevalence and projected to become the leading cause of death of all humans, myriad prevention and treatment avenues have been studied. Growing evidence suggests that in addition to lifestyle modifications, smoking cessation, and medical therapy, dietary compounds and supplements may play a significant role in the treatment of this disease process.

In modern day society, however, including these compounds in their recommended doses from food is becoming increasingly difficult. These dietary supplements may have a role in altering lipid profiles, improving hypertension, treating hypercoagulable states, and reducing the inflammation that leads to atherogenesis amongst other effects.

As more research is done in this continuously expanding field of knowledge, natural compounds will continue to provide new insights and novel therapies in our fight against CVD.

Written with exclusive rights for Pure Prescriptions, Inc.