The Secret to Clean Arteries By Michael A. Smith, MD 

 Paraoxonase-1, better known as PON-1, is the secret to clean arteries. This enzyme plays a critical role in protecting arteries from plaque build-up by enhancing the removal of cholesterol from the walls of arteries. PON-1 is attached tohigh-density lipoproteins (HDL). PON-1 does more than just cleanse arterial walls of plaque, it also protects against lipid oxidation. Oxidized fats and cholesterol are more prone to stick to artery walls, creating unstable plaques. Unstable plaques rupture, causing rapid occlusion of blood flow to vital organs such as the heart and brain. 

PON-1 helps to stabilize plaques by inhibiting chronic inflammation and platelet activation—factors that can all lead to plaque rupture.

As humans age, PON-1 levels markedly decline, thereby reducing the ability of HDL to protect against heart attack and stroke. This phenomenon helps explain the onset of acceleratedatherosclerosis; where within a period of only a few years, an aging person’s healthy arteries rapidly occlude with plaque.

The age-related reduction in PON-1 may also explain studies showing that statin drugs lose their benefit in certain aging populations, since the effects of statins are no longer sufficient to protect against the multiple factors involved in the development of atherosclerosis in the elderly.1-3

How to Boost PON-1 Activity

1. Pomegranate

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.4

2. Resveratrol

Strong evidence has recently emerged for several compounds with known cardio-protective 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. Red wine polyphenols increase PON-1 activity and reduce LDL oxidation.

Resveratrol is the best-known of the red wine polyphenols. It exerts powerful control over the PON-1 gene, increasing PON-1 expression in human liver cells and protecting against atherosclerosis in animal models.5

3. Quercetin

Quercetin is another polyphenol found in red wine and many other plant sources. It also up-regulates PON-1 gene expression, protecting against fat and cholesterol oxidation.

Quercetin possesses numerous mechanisms that help stabilize and preserve PON-1 activity against oxidative stress.6


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  2. Kekes E. Combined antihypertensive and antilipemic therapy as one of the pillars in the poly-pharmacologic preventive strategy for patients with high cardiovascular risk. Orv Hetil. 2008 Sep 28;149(39):1827-37.

  3. Gouedard C, Koum-Besson N, Barouki R, Morel Y. Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol. 2003 Apr;63(4):945-56.

  4. Aviram M, Dornfeld L, Rosenblat M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000 May;71(5):1062-76.

  5. Do GM, Kwon EY, Kim HJ, et al. Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun. 2008 Sep 12;374(1):55-9.

  6. Aviram M, Rosenblat M, Billecke S, et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999 Apr;26(7-8):892-904.