The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 12 No.
6 • October 2009
You Can Increase Your Paraoxonase 1 (PON 1) Gene
Expression to Protect Against Cardiovascular
Disease and HDL and LDL Oxidation
Another important health protecting molecule that is being intensively investigated is paraoxonase 1 (PON 1), an enzyme associated with high-density lipoprotein (HDL) that is mainly secreted by the liver. The many health effects of PON 1 include: importantly, prevention of the oxidation of HDLs (which can destroy HDL’s protective properties such as its anti-oxidative and anti-inflammatory effects);* prevention of the oxidation of LDL (which promotes atherosclerosis); and hydrolysis of platelet-activating factor, which is involved in vascular disease and other inflammatory conditions. As the authors suggest: “Therefore, pharmacological modulation of PON-1 activity or PON-1 gene expression could constitute a useful approach for the prevention of CVD [cardiovascular disease] and OP [organophosphate poisons] intoxication.” OPs are found in some insecticides (parathion, chlorpyrifos) and also some chemical warfare agents. PON-1 can hydrolyze (and, thus, detoxify) OPs.
Low activity of PON 1 has been reported in disease conditions that include renal (kidney) disease, diabetes, HDL deficiencies, and liver cirrhosis. High fat diets have been reported to decrease PON 1 activity, while moderate alcohol consumption increased it. PON 1 is significantly decreased (and remained lower than baseline for up to 8 hours) in humans after a meal rich in used cooking fat (such as fat used to deep-fry foods prepared at fast food restaurants). The latter study was conducted with 12 healthy male subjects aged 22 to 63 who were randomized to receive a milkshake containing either fat that had been used for deep-frying (yuck!) or the same type of fat that had not been previously used. PON 1 has been shown to be protective in oxidative stress (including cardiovascular disease), Alzheimer’s disease, metabolic syndrome, and liver diseases.
Dietary Factors That Increase PON 1
PON 1 is increased following consumption of polyphenol-rich diets. Wine consumption and some polyphenols present in wine or fruit juice were reported to increase PON 1 in humans and mice. In one study, naringenin, flavone, and quercetin increased PON 1 mRNA about twofold in cell culture, but catechin was a poor inducer. In another paper, oleic acid (usually consumed in the form of olive oil, but high oleic sunflower oil contains considerably more oleic acid) was reported effective in an in vitro study in protecting PON 1 activity from oxidative stress. Moderate alcohol (40 g/day in men and 30 g/day in women) had a modest effect, increasing serum HDL cholesterol by 6.5% and PON 1 by 3.7%. A daily consumption of pomegranate juice for 1 year by patients with carotid artery blockage induced an increase in serum PON 1 activity and also decreased the amount of oxidized LDL and progression of atherosclerosis (measured by the degree of carotid intima-media thickness). Resveratrol has also been reported to induce PON 1 gene expression in a human hepatocyte (liver) primary culture and in the HuH7 hepatoma cell line and in other human cell lines, as well as in apolipoprotein E-deficient mice (a commonly used animal model of atherosclerosis).
As we have long noted, advances in understanding of the physiological effects of foods and food components has resulted in the development of a virtual parallel medical system (parallel that is to the FDA’s xenobiotic drugs-only system enforced by FDA censorship of truthful information on the labels and advertising of dietary supplements and foods). Keep yourself informed! Also, you can follow our latest involvement in suing the FDA over its egregious suppression of the First Amendment guarantee of free speech (“Congress shall make NO law . . . abridging the freedom of speech”) (emphasis added) at www.emord.com.* We have been very lucky in getting good judges in our earlier cases against the FDA (especially, the landmark decision in Pearson v. Shalala, U.S. Circuit Court of the D.C. Circuit, 1999) and can only hope that it happens again, especially at the Court of Appeals level.
- Gouedard et al. Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol Cell Biol 24(12):5209-22 (2004).
- Camps et al. Pharmacological and lifestyle factors modulating serum paraoxonase-1 activity. Mini Rev Med Chem 9:911-20 (2009). [This paper also reported increased PON 1 in some human clinical studies of statins and fibrates, as well as a study of orlistat (a gastrointestinal lipase inhibitor) in obese humans.]
- Sutherland et al. Reduced postprandial serum paraoxonase activity after a meal rich in used cooking fat. Arterioscler Thromb Vasc Biol 19:1340-7 (1999).
- Sierksma et al. Kinetics of HDL cholesterol and paraoxonase activity in moderate alcohol consumers. Alcohol Clin Exp Res 26:1430-5 (2002).
- Aviram et al. Pomegranate juice consumption for 3 years by patients with carotid stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 23:423-33 (2004).
- Gouedard et al. Induction of the paraoxonase-1 gene expression by resveratrol. Arterioscler Thromb Vasc Biol 24:2378-83 (2004).
- Curtin et al. Resveratrol induces catalytic bioscavenger paraoxonase 1 expression and protects against chemical warfare nerve agent toxicity in human cell lines. J Cell Biochem 103:1524-35 (2008).
- Do 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 374:55-9 (2008).