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Enhance Endothelial Health

Despite billions of dollars spent every year on cholesterol-lowering statin drugs like Lipitor® and Crestor®, cardiovascular disease continues to be the leading killer worldwide.1,2 Clearly, just lowering your cholesterol is not the entire solution, otherwise, the epidemic of heart disease would be over.

Overlooked by mainstream medical practice is the essential role that the endothelium plays in protecting cardiovascular health. The endothelium is the one-cell-thick layer that lines all of your blood vessels, down to the smallest capillaries.3,4

Pomegranate extracts are proving to be an effective means of protecting our delicate endothelium. Studies show that pomegranate works on a number of levels to ensure cardiac health by reducing cellular cholesterol accumulation, protecting LDL from oxidation, and in lab studies, shrinking atherosclerotic plaque.5-7 In addition, pomegranate promotes supple arteries that maintain healthy blood flow and pressure to all of your tissues and organs.7,8

Best of all, research concludes that by improving endothelial health, pomegranate supplementation lowers risk factors for heart attacks, strokes, and other cardiovascular events.8-10



The Importance Of Endothelial Health

Your chances of having a heart attack or a stroke depend a great deal on the health of your endothelium.3,4 The endothelial cells use nitric oxide to signal the need for relaxation to arterial muscle cells.

As we age and develop pathological conditions such as atherosclerosis, our ability to produce and respond to nitric oxide rapidly diminishes.11-13 Aging humans generate more oxidative and inflammatory molecules that deplete nitric oxide production.13,14

The result is endothelial dysfunction, a serious condition that leads to arteries “stiffening” and losing their ability to respond to changes in blood flow and pressure. Endothelial dysfunction is often initiated as a result of oxidative stress.3 A major cause of damage in arterial walls is oxidation of LDL (low-density lipoprotein).15 Oxidized LDL is taken up by specialized receptors on endothelial cells to form atherosclerotic plaques.11,12

In a vicious cycle, chronic inflammatory reactions cause further oxidant damage, which results in further reduction in nitric oxide availability, and finally, further reduction of endothelial control over blood flow and pressure.3 This cycle sets the stage for high blood pressure and all the cardiac events that can result from this condition.3

Statin drugs are prescribed by physicians to reduce overall cholesterol production, thereby lowering LDL levels and helping to prevent further growth of plaques and inflammatory changes.16,17 Too often, however, statin therapy is initiated after dangerous changes have occurred in the endothelium and muscular walls of arteries.

Fortunately, extensive research demonstrates that pomegranate extracts enhance the body’s natural protective responses to prevent endothelial dysfunction, promote healthy mechanisms, and even remove oxidized LDL from arterial walls.



FACTORS OF REDUCED ENDOTHELIUM-DEPENDENT DILATION13,18

Listed below are the factors that contribute to impaired endothelial-dependent dilation, resulting in arteries that are stiff and relatively unresponsive to changes in blood flow and pressure, which ultimately triggers stroke and heart attack.

Increased production of superoxide and other reactive oxygen species in aging
Upregulation of oxidant-producing enzymes (e.g., NADPH oxidase)
Increased bioactivity of artery-constricting endothelin-1
Reduced endothelial production of/responsiveness to artery-dilating compounds
Development of vascular inflammation
Formation of advanced glycation endproducts (AGEs)
Increased rate of endothelial cell apoptosis(programmed cell death)
Reduced expression of estrogen receptor alpha (in postmenopausal women)



Pomegranate Boosts Your Body’s Defenses

Your body has natural mechanisms to protect your cardiovascular health, but they become weakened and ineffective over time.

For example, your body is equipped with specialized mechanisms that move cholesterol from tissues back to the liver for clearance.19 It also has specialized protein complexes that protect cholesterol from oxidizing to cause plaques. It even has its own specialized mechanisms for mopping up destructive free radicals like superoxide that promote oxidation and inflammation, and reduce vital supplies of artery-dilating nitric oxide.20-24

Pomegranate extracts directly aid your own body’s defense mechanisms and prevent catastrophic outcomes. Pomegranate extracts:

Enhance cholesterol outflow from inflammatory white blood cells, helping to reduce the risk of plaque formation.5,6,25
Protect vulnerable LDL molecules from the oxidation that leads to arterial wall inflammation and promotes plaque generation.6,7
Boost natural antioxidant systems, particularly superoxide dismutase (SOD), protecting vital nitric oxide and allowing the endothelium to recover from the effects of chronic oxidative and inflammatory stresses.26-28 (See sidebar on page 56 for additional benefits of supplementing directly with SOD.)



Endothelial Dysfunction

Your endothelium is a super-thin layer of cells lining the arteries that control blood flow and pressure.
But the endothelium’s regulatory abilities fade with age, the victims of ever-present oxidant stress and inflammation.
Poor endothelial health is the primary factor in the development of stiff, unresponsive, atherosclerotic arteries, which leads to heart attacks and strokes.
Pomegranate extracts contain a host of natural molecules that gently assist your body in restoring its own natural endothelial defense mechanisms.
Pomegranate extracts protect LDL cholesterol from dangerous oxidation, and enhance activity of the body’s antioxidant mechanisms.
Studies show that pomegranate supplementation improves endothelial health, which may reduce the risk for heart attacks, strokes, and other cardiovascular events.
Adding an oral superoxide dismutase (SOD) supplement further promotes endothelial defense by bolstering natural antioxidant mechanisms.
Some members use formulas that provide standardized pomegranate and a special SOD-boosting compound that is protected against degradation in the digestive tract.



Pomegranate’s Endothelial Defense Mechanisms

Pomegranate contains a number of extremely potent antioxidant molecules including tannins and anthocyanins, which have been shown to exert important endothelial-protective, anti-atherosclerosis effects.7,29 Pomegranate’s multiple therapeutic targets include those dangerous oxidized LDL particles and the inflammatory white blood cells that stream into developing plaques, eventually causing them to block arteries and cause heart attacks or strokes.5,7,29

Pomegranate contains particularly potent polyphenols that protect against LDL and HDL oxidation, which helps minimize endothelial dysfunction in its earliest stages.7

A unique property of pomegranate is its ability to boost activity of a beneficial enzyme called paraoxonase-1 (PON-1), which is found in beneficial HDL and accounts for many of its “good cholesterol” features by breaking down oxidized lipids, even those that have already been taken up into plaques.5,7

In a mouse model of coronary heart disease, treatment with pomegranate extract had a number of benefits to reduce atherosclerotic plaque.30 The size of atherosclerotic plaques in the animals’ aortas shrank, and the proportion of coronary arteries clogged with plaques was markedly reduced. Inside the plaques, researchers found substantial reduction in oxidative stress, inflammatory signaling molecules, and inflammatory white blood cells. And treated animals’ hearts remained normal in size, not enlarging and developing electrocardiogram (ECG) abnormalities as in control animals.30

In a rat study, researchers administered the cancer chemotherapy drug doxorubicin, which has cardiotoxic effects that mimic some of the damage seen following a heart attack. Doxorubicin also produces intense oxidative stress.31,32 The group given doxorubicin plus a whole-fruit extract of pomegranate had less pronounced ECG abnormalities and beneficial reductions in heart rate compared to the group that was only given the drug. Chemical analysis of their blood revealed significant decreases in the markers of muscle damage creatine kinase (CK-M and lactate dehydrogenase (LDH). Levels of the beneficial antioxidant glutathione rose significantly in treated animals as well. Microscopic examination of heart tissue demonstrated protection against muscle cell damage caused by the drug.

The previous two studies show pomegranate’s great promise in preventing atherosclerosis and protecting heart muscle from oxidant damage. A third study, however, illustrates that pomegranate juice can, in fact, slow development of even advanced atherosclerosis. Here, scientists used young mice genetically programmed to develop atherosclerosis, treating them with pomegranate juice or placebo for two months.5 Pomegranate juice intake led to increased PON-1 activity, which protects the function of HDL in transporting cholesterol out of arteries and back to the liver for disposal. PON-1 also reduced the amount of oxidized LDL taken up by 31% in certain inflammatory white blood cells compared with controls.

Remarkably, pomegranate supplementation also increased the rate of cholesterol flow out of those immune cells by 39%. Compared with placebo-treated mice, supplemented animals had a reduction in the size of plaques in their arteries of 17%. This is the first study to show so clearly that pomegranate juice supplementation is capable of attenuating the development of even advanced atherosclerosis.5

A late 2013 study reveals still more about the potential role of pomegranate juice and extracts in protecting endothelial health. An early stage in the development of atherosclerosis is the accumulation of oxidized LDL in inflammatory cells called macrophages. Israeli scientists found that by adding pomegranate juice to such inflammatory cells in combination with a statin drug (simvastatin), they could significantly improve the statin’s ability to block production of cholesterol in the cells.33 Moreover, pomegranate increased the statin’s ability to diminish oxidative stress. These results reveal the tremendous potential for pomegranate to supplement existing benefits of statins, perhaps allowing lower doses of these synthetic drugs.33