Life Extension Magazine July 2007
Reversing Atherosclerosis Naturally
By Dale Kiefer
By Dale Kiefer
Life Extension Magazine July 2007
By Dale Kiefer
Scientists have discovered a natural ingredient derived from a species of melon that has been shown to reverse signs of atherosclerosis in aging blood vessel walls. This nutritional supplement is able to boost levels of the body’s most powerful antioxidant defense enzyme, superoxide dismutase (SOD).
A comparison of two recently-published clinical trials shows that this natural supplement not only reversed signs of atherosclerosis in human blood vessel walls, but that it did so better than a leading multibillion dollar prescription statin drug. Just eight months ago, Life Extension members were enlightened to the ability of pomegranate to reverse signs of atherosclerosis. This specialized melon extract, together with pomegranate, offers aging humans a powerful new weapon in the battle to reduce the risk of heart attack and stroke by restoring healthy function to aging arteries.
Atherosclerosis: the Silent Enemy
Even people who have no symptoms of cardiovascular disease may be developing silent, progressive atherosclerosis as they grow older. Derived from Greek words meaning “hard paste”, atherosclerosis is a chronic inflammatory condition affecting the interior of the arteries, which become stiff, clogged, and dysfunctional. Consisting of cholesterol, cellular debris, and other components, atherosclerotic plaque blocks the flow of vital oxygen and nutrients to tissues throughout the body.
Atherosclerosis is believed to begin when the delicate inner arterial lining—the endothelium—is damaged and becomes dysfunctional; possibly beginning as early as childhood.1 Sticky, fatty substances, such as low-density lipoprotein (LDL), fibrinogen, and triglycerides adhere to the endothelial lining and begin to trap other components, including calcium. The plaque may cause a rupture in the arterial wall, allowing a blood clot to form. Clots can block local blood flow completely, or they may break free and cause dangerous blockages elsewhere. When such blockages occur in the vessels supplying the heart, for instance, a heart attack occurs. Deprived of oxygen, cardiac muscle dies quickly; when a blockage affects the blood supply to the brain, a stroke may result.
The Superoxide Radical and Endothelial Dysfunction: Danger to Aging Arteries
Damage to cells that line our arteries is a critical initiating event in atherosclerosis, a leading cause of heart attack and stroke. As the delicate endothelium (inner arterial wall) becomes weakened, toxic substances circulating in the blood pass through the endothelial cell layer and become oxidized. This oxidation induces chronic inflammation that leads to thickening of the blood vessel wall and subsequent atherosclerosis. Depending on a person’s individual risk factors (such as poor diet, lack of exercise, high homocysteine, high levels of inflammation, smoking, high blood pressure, and the aging process itself), oxidized lipids continue to accumulate in the endothelium, and the atherosclerotic process accelerates.
Scientists know that oxidative stress is a crucial, causal factor in endothelial dysfunction, which itself is a key initiating event for abnormal blood vessel wall thickening and atherosclerosis. Cutting-edge research shows that superoxide dismutase, the body’s most important antioxidant defense enzyme, plays an important role in maintaining healthy endothelial function by quenching dangerous superoxide radicals.
The superoxide radical inactivates the crucial vasodilator nitric oxide and compromises endothelial function.2,3 Furthermore, rapid improvement in endothelial function and regression of atherosclerosis is associated with reduction of the dangerous superoxide radical in the arterial wall.4 New research shows that the superoxide radical plays a role in hypertension associated with kidney disease, oxidative vascular stress associated with accelerated atherosclerosis in diabetes, and heart failure in humans.5-8
Statin Drugs and Atherosclerosis
In the past, numerous studies have examined the effects of cholesterol-lowering statin drugs on atherosclerosis using proven ultrasound technology that measures for pathological thickening (intima-media thickness, or IMT) of the aging blood vessel wall. Interestingly, most large statin drug trials show only slowing of progression, rather than regression of atherosclerosis, as measured with this highly-respected technology.
For example, the 1998 REGRESS study showed slowing of progression of atherosclerosis, but not regression, with the statin drug pravastatin (Pravachol®).16 The 1995 KAPS study also showed that
pravastatin produced a significant slowing of progression of atherosclerosis, but not regression.17 Although the ASTEROID study showed evidence of regression of atherosclerosis in high-risk patients, this study used the very potent statin drug, rosuvastatin (Crestor®).18 Another head-to-head comparative study (ARBITER) showed slight regression of IMT with a high dose of the potent drug atorvastatin (Lipitor®).19 However, many “in the know” unbiased medical experts have raised questions about the results of this study, commenting on data handling and methodological issues used by the Pfizer-sponsored investigators.
Recently, a clinical trial published in the influential Journal of the American Medical Association indicated that the cholesterol-lowering statin drug, Crestor® (rosuvastatin), is capable of slowing the progression of silent subclinical atherosclerosis. As expected, over the course of two years, a high dose (40 mg) of the very potent statin drug Crestor® significantly lowered harmful lipid levels. But it merely slowed or halted atherosclerosis progression—it did not produce regression. In the investigators’ own words: “Rosuvastatin [Crestor®] did not induce disease regression.”20
In sharp contrast, a nutritional supplement derived from a unique species of melon was shown recently to not only halt IMT progression in apparently healthy adults, but to significantly reverse its progression over the course of two years.21
Oral SOD Reverses IMT
Impressive new research indicates that a patented form of the natural antioxidant superoxide dismutase (SOD) significantly reverses the IMT thickening process, long before atherosclerosis becomes life-threatening.21 Known as the “enzyme of life” when it was first discovered in the late 1960s, SOD is considered the body’s most important antioxidant defense enzyme. Its powerful benefits include the ability to activate and regenerate other key native antioxidants, such as glutathione peroxidase and catalase. By itself, SOD disarms the extraordinarily reactive superoxide radical. It accomplishes this feat with lightning speed, thus preventing superoxide from wreaking havoc with important biological tissues, including the delicate vascular endothelium.
Scientists have long sought a way to boost levels of SOD as a natural means of combating the oxidative damage that lies at the root of so many degenerative disease processes, including atherosclerosis.21 Noting that certain varieties of cantaloupe had an exceptionly long shelf life, food scientists found that these melons provided an exceptionally rich source of SOD. Still, this SOD remained stubbornly unavailable to the body when consumed orally. Until, that is, French researchers pioneered a method to “cloak” a natural melon-derived SOD molecule with gliadin (a simple protein derived from wheat), protecting it from the harsh acidic environment of the stomach and intestines long enough for the bioactive SOD enzyme to be absorbed intact into the bloodstream.22,23Dubbed GliSODin®, this compound has been thoroughly documented to be a particularly potent orally bioavailable form of SOD. Many competing products purporting to contain SOD are simply ineffective. Without the protection of the gliadin molecule, most SOD supplements are destroyed by the digestive tract long before they can benefit the body, rendering them ineffective as oral supplements.
Clinical Study Confirms Efficacy of GliSODin® for Regression of Atherosclerosis
In a groundbreaking new study, investigators led by Professor Maurice Cloarec from the French National Association for Medical Prevention showed that oral supplementation with GliSODin® was associated with regression of atherosclerosis in middle-aged adults (ages 30-60), as determined by ultrasonography. This finding is especially exciting, in that atherosclerosis progression was not slowed, nor halted, but rather that it was actually reversed.
The scientists began this study by recruiting adults with risk factors for atherosclerosis, including a family history of stroke, elevated blood pressure, elevated blood lipids and blood sugar, and a height-to-weight ratio above normal. Subjects received instruction in following a standardized, heart-healthy, Mediterranean-type diet, and were given counseling regarding lifestyle modifications.
A baseline IMT reading was performed, and assessments were also made of individuals’ antioxidant status and blood lipid levels, among other health parameters. All subjects first adhered to a new, healthier diet for one year. At the end of the first year, the scientists documented “minor improvements” in blood pressure, body mass index (BMI), and LDL levels among all subjects. These improvements were attributed to the healthier diet and lifestyle modifications. Subjects’ antioxidant status, however, remained poor. Furthermore, subjects’ IMT values remained unchanged. Investigators noted that the IMT numbers were, “too high…considering the age of these subjects”.21
At this point, a total of 34 subjects were randomly divided into two groups. One group continued with the amended diet, while a second group continued the diet while also taking 500 IU of GliSODin® daily. Subjects’ progress was then monitored for two additional years. During this phase, parameters such as blood pressure, BMI, and LDL levels remained largely unchanged among all subjects. But about nine months after beginning GliSODin® treatment, significant improvements in antioxidant status were documented in the treatment group. Antioxidants monitored included blood SOD levels and blood glutathione peroxidase levels. Levels of malondialdehyde (a biomarker for oxidative stress24) were also documented. The antioxidant status of control subjects, who were not taking the supplement, remained essentially unchanged.