How Aging Humans Can Slow and Reverse Atherosclerosis
By Richard Hathaway
How to Boost Your PON-1 Levels
The most recent research indicates that pomegranate and its extracts can significantly elevate levels of PON-1 activity in the body. Pomegranate does this through a number of distinct biomolecular pathways that include combating inflammation and LDL adhesion and favorably modulating gene expression.
Pomegranate extracts reduce oxidation and inflammation largely through their effect on PON-1 activity, intervening at each step in the development of atherosclerosis.33
Atherosclerosis begins with oxidation of LDL cholesterol. Damaged LDL “clumps” together and accumulates in specialized immune system cells called foam cells. The foam cells invade blood vessel walls, triggering inflammatory responses and the formation of early atherosclerotic plaque.
Inflamed plaque attracts clot-forming platelets, leading ultimately to a narrowing of blood vessels that restricts blood flow. When inflamed plaques rupture—or clots form that block blood flow entirely—tissue dies, producing a heart attack or stroke, depending on location.
A dedicated group of Israeli researchers led the way in detailing how pomegranate disrupts atherosclerosis formation at each of these developmental phases—and the crucial role PON-1 plays in this process. They began with a landmark study in 2000 that focused on pomegranate’s antioxidant properties.
The team started with a group of healthy male volunteers, along with laboratory mice genetically engineered to develop atherosclerosis.33 When human subjects consumed pomegranate juice for 2 weeks, the researchers found dramatic reductions in LDL “clumping” and retention in vessels, accompanied by a 20% increase in PON-1 activity. In the atherosclerosis-prone mice, a 90% reduction in oxidation of LDL cholesterol was seen. Supplemented mice also developed atherosclerotic lesions 44% smaller than unsupplemented controls, an effect attributed to reduction in the number of inflammatory foam cells.
The Israeli researchers went on to show that concentrated pomegranate extract and pomegranate juice induced profoundly protective effects—even in mice with advanced atherosclerosis.34 Pomegranate not only reduced accumulation of oxidized fat in macrophages within cells—it reversed it, boosting the outflow of cholesterol by 39%! In other words, pomegranate may be able to interrupt and even reverse atherosclerosis, not just prevent it.
After the Israeli group’s landmark discoveries, additional supportive evidence emerged. The scientists found that pomegranate polyphenols accumulated inside of the arterial macrophages (immune cells) that absorb LDL cholesterol, preventing them from oxidizing their LDL burden and keeping them from turning into dangerous foam cells.35 They also observed that pomegranate-induced elevation in PON-1 activity stimulated the breakdown of existing oxidized LDL cholesterol—even in atherosclerotic plaques that have already formed.
Additional findings of interest were evinced in patients with carotid artery stenosis,36 a narrowing of the main blood vessels supplying the brain. These individuals are at very high risk for stroke.
After one year, patients in this study given pomegranate experienced an 83% increase in PON-1 levels and their oxidized LDL levels consequently fell by a remarkable 90%. The placebo group worsened by 9% whereas carotid artery narrowing was reversed by 30% in the pomegranate supplemented patients. This translates to a significant increase in blood flow to the brain in those using pomegranate. Both groups continued taking their conventional medications.36
PON-1’s capacity to powerfully inhibit lipid peroxidation in this pomegranate study cohort appears to have resulted in substantial reduction in stroke risk for patients with atherosclerosis. Other benefits were seen as well: serum levels of antibodies directed against oxidized LDL (important contributors to the inflammatory component of atherosclerosis) fell by 19%, while total plasma antioxidant status rose by an astounding 130%. Systolic blood pressure was also reduced by 12% in supplemented patients over the course of a year.36
Evidence has also come to light for PON-1’s role in diabetes management through pomegranate consumption. When patients with type 2 diabetes were compared to healthy controls, their PON-1 levels were found to be depressed by 23%. When these same patients were given pomegranate juice (50 mL/day for 3 months), their serum PON-1 activity rose by 24%, helping restore it to healthy levels.37
In 2007, researchers discovered pomegranate polyphenols upregulated genes for PON-2 in LDL-scavenging macrophages.38 PON-2 is a molecule closely related to PON-1 that exerts similarly beneficial effects. The resulting increase in production of PON-2 directly improved these cells’ oxidative status.
Upregulation of PON-1 genes has also been documented in liver cells exposed to pomegranate polyphenols—a critical benefit, since liver cells are responsible for PON-1 production.39 In the past few years researchers have also demonstrated that pomegranate stabilizes PON-1’s molecular bond with beneficial HDL. PON-1 molecules can degrade over time, detaching from the “mother” HDL molecule. Pomegranate extracts have been shown to strengthen and support the molecular bond between PON-1 and HDL complexes—thereby protecting HDL from oxidative decay.40,41
Other PON-1 Enhancers
Strong evidence has recently emerged for several compounds with known cardioprotective effects that may also favorably increase your PON-1 levels. Moderate consumption of wine, beer, and spirits is associated with an increase in PON-1 activity.42 Red wine polyphenols increase PON-1 activity and reduce LDL oxidation.16,43,44 Specifically, resveratrol, the best-known of the red wine polyphenols, exerts powerful control over the PON-1 gene, increasing PON-1 expression in human liver cells and protecting against atherosclerosis in animal models.45,46 (The liver is where PON-1 is produced in the body.)
Quercetin, another polyphenol found in red wine and many other plant sources, also upregulates PON-1 gene expression, protecting against LDL oxidation.47 Quercetin also possesses numerous mechanisms
pomegranate,it helps stabilize and preserve PON-1 activity against oxidative stress.48
Lipid peroxidation—free radical damage to healthy cell membranes—is a primary aging factor implicated in the onset of numerous degenerative diseases. PON-1 (paraoxonase-1) is an under-recognized enzyme attached to beneficial HDL that has been shown to block lipid peroxidation. Recent research suggests that PON-1 may serve as a formidable defense against numerous diseases of aging, including heart disease, metabolic syndrome, arthritis, and certain cancers.26,29,32,49,50 PON-1 levels decrease with advancing age, contributing to a decline in the cardioprotective effect of HDL. Pomegranate has been shown to elevate PON-1 activity and support its activity in the body. It has been shown to upregulate the gene that governs PON-1 production, increasing its output in liver cells and elevating its concentration in the blood. Pomegranate extracts protect and sustain PON-1 activity at the molecular level, preventing its degradation, and maintaining its bond within the HDL molecular complex. Emerging evidence suggests that resveratrol and quercetin may exert similar effects on PON-1 levels and activity.
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