The Secret to Clean Arteries

The Secret to Clean ArteriesParaoxonase-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 to high-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 accelerated atherosclerosis; 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

References

  1. Okumachi Y, Yokono K. Anti-aging medicine: the evidence to the value of the antihypertensive drugs, hypoglycemic drugs and statins. Nippon Rinsho. 2009 Jul;67(7):1372-6.
  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.

Resveratrol May Reverse Arterial Aging

Resveratrol

“Atherosclerosis is reversible” is not a phrase we expected to hear from mainstream medical researchers until very recently—since these are the precise opening words of a remarkable editorial about resveratrol that appeared in a recent issue of the prestigious New England Journal of Medicine. Just as astonishingly, the editorial was written by a renowned immunologist, Linda K. Curtiss, PhD, of the Scripps Research Institute in La Jolla, California. The fact that an immunologist is writing about cardiovascular disease in a trend-setting medical journal speaks volumes about how far we have come in our understanding of chronic diseases and their relationships with inflammation, which is an immune system phenomenon. What truly sets Dr. Curtiss’s article apart, though, is her description of a dramatic new phenomenon mediated by the grape polyphenol resveratrol.

Curtiss’s excitement comes from work done by Cleveland Clinic cell biologist Young-Mi Park, MD, who was exploring the role of oxidant stress and inflammation on the pathogenesis, or disease-causing mechanisms, of atherosclerosis. Knowing that fat-laden inflammatory cells called foam-cell macrophages trigger inflammation when they become trapped beneath the lining of blood vessels, Park’s team sought to understand why the cells become trapped, and how they could be freed from their “endothelial bondage,” thereby reversing the inflammatory process.

The most natural approach to take, Park’s group decided, was simply to test known antioxidants’ ability to prevent the foam cells from migrating into the endothelial lining in the first place, and their ability to release any cells that were already present. Specifically, they studied how oxidized low-density lipoprotein (LDL) promotes foam-cell formation and impairs migration. To do this they blocked LDL oxidation with several potent antioxidants. They found that oxidized LDL actually triggered production of a sort of cellular “glue” in the form of filaments of actin, one of the proteins also found in muscle tissue. The actin filaments were entangling the foam cells, preventing their natural migration out of the endothelial lining, leading to progressive inflammatory changes.

Park’s group chose resveratrol as one of the two antioxidants to test—another testimony to the respect that mainstream researchers are according this remarkable molecule (the other was N-acetylcysteine, also an antioxidant available in supplement form). Resveratrol treatment of the foam cells inhibited production of reactive oxygen species by greater than 90%, an important first step in breaking the cycle. Even more impressively, resveratrol supplements partially restored the foam cells’ ability to move out of the entangling actin filaments, and migrate away from the endothelial lining!

This brings us back to Dr. Curtiss’s astounding initial observation that atherosclerosis is a reversible condition—through the use of powerful antioxidants such as resveratrol, we can now understand how oxidized LDL contributes to invasion of endothelium by inflammatory cells, and how prevention or reversal of LDL oxidation promotes mobilization of inflammatory cells and their emigration away from vessel linings.

As Dr. Park concluded, “[these studies] also provide additional mechanistic support for the atheroprotective effect of antioxidants.” Resveratrol is already well-known as a cardiovascular protective supplement—the work of Park and others is now showing us that resveratrol must also be considered a valuable cardiovascular therapeutic supplement, one that can literally “turn back the clock” on chronic vascular diseases of aging!

Vitamin D deficiency: emerging cardiovascular disease risk factor

emerging cardiovascular disease risk factor

A review published in the December 9, 2008 issue of the Journal of the American College of Cardiology describes the involvement of deficient vitamin D levels in common risk factors for cardiovascular disease (including high blood pressure, diabetes, and obesity) and in cardiovascular events.

Vitamin D deficiency is estimated to affect up to half of all adults and 30 percent of children in the United States. While the vitamin’s role in bone health has long been known, a flurry of recent studies have uncovered associations between deficient levels of the vitamin and a number of diseases, including cardiovascular disease. In their review, Michael F. Holick, MD, PhD and colleagues note that insufficient levels of vitamin D activate the renin-angiotensin-aldosterone system, which can lead to hypertension and thickening of the heart and blood vessel walls. Altered hormone levels related to a deficiency of vitamin D (which is also a hormone) increase the risk of diabetes, which is a well known risk factor for the development of cardiovascular disease. In 15,088 subjects from the NHANES III national cohort registry, higher vitamin D levels were related to a lower risk of diabetes as well as hypertension, high triglycerides, and obesity. And among Framingham Heart Study participants who had levels of vitamin D of less than 15 nanograms per milliliter upon enrollment, the risk of subsequent cardiovascular events was twice as great as the risk experienced by those with higher levels of the vitamin.

Chronic vitamin D deficiency is associated with secondary hyperparathyroidism, which increases the risk of inflammation and cardiovascular events. Elevated parathyroid levels were associated with an increased risk of death among older individuals compared to those with normal levels over the course of follow-up in a recent observational study.

“We are outside less than we used to be, and older adults and people who are overweight or obese are less efficient at making vitamin D in response to sunlight,” stated review coauthor James H. O’Keefe, MD, who is a cardiologist and director of Preventive Cardiology at the Mid America Heart Institute in Kansas City, Missouri. The authors’ strategy for restoring vitamin D to optimal levels in cardiovascular disease patients includes initial treatment with 50,000 international units (IU) vitamin D2 or D3 weekly for 8 to 12 weeks followed by maintenance with 1,000 to 2,000 IU daily. They also suggest limited sun exposure as a means of increasing vitamin D. They observe that supplementation with vitamin D is safe and that such effects as elevated calcium levels and kidney stone development have only rarely been observed among individuals who consume 20,000 IU per day or more.

“Vitamin D deficiency is an unrecognized, emerging cardiovascular risk factor, which should be screened for and treated,” stated Dr O’Keefe. “Vitamin D is easy to assess, and supplementation is simple, safe and inexpensive.”

“Restoring vitamin D levels to normal is important in maintaining good musculoskeletal health, and it may also improve heart health and prognosis,” Dr. O’Keefe concluded. “We need large randomized controlled trials to determine whether or not vitamin D supplementation can actually reduce future heart disease and deaths.”