In 1946, famed biochemist Abraham Mazur was the first to report the presence of an enzyme in animal tissues which could hydrolyze organophosphates (OP).(1) Organophosphates are a class of man-made poisons that are primarily used in herbicides, pesticides, and insecticides.  They are also are also the main components of nerve gas, a chemical warfare agent still present in military stockpiles of several nations, including the United States.

The most commonly used organophosphate pesticides are the following:

  1. Parathion
  2. Chlorpyrifos
  3. Diazinon
  4. Dichlorvos
  5. Phosmet
  6. Fenitrothion
  7. Tetrachlorvinphos
  8. Azamethiphos
  9. Azinphos-Methyl
  10. Malathion
  11. Methyl Parathion
Exposure to organophosphates is typically thought to be via food products such as wheat, flour, and cooking oil, as most conventionally grown grains are sprayed. However, current thought expands the possible exposure to these toxins to vegetables, fruits and even organically foods due to cross contamination. Ant and roach spray might also be a potential source of exposure. Fields sprayed with such poison will dissipate over several years post stopping its use however, few studies exist on the toxicity to humans and the cellular damage that may persist over time.
Abraham Mazur’s discovery of the enzymatic pathway that helps rid these chemicals from the body ultimately led to the identification of human serum paraoxonase (PON1) enzyme in early 1950’s. PON1 was identified to hydrolyze the organophosphates such as paraoxon, and oxon metabolite of chlorpyriphos, diazinon and nerve gases (e.g., sarin and soman), helping the body detoxify such poisons both intracellularly and through the Phase 2 pathway in the liver. Since PON1 was initially characterized as organophosphate hydrolaze, it still derives its name from its in vitro used substrate, paraoxon.
Recently, in addition to its role in hydrolyzing organophosphorus compounds, PON1 has been shown to play an important role in lipid metabolism and thus in atherosclerosis and cardiovascular disease.(2) Among is many functions, PON1 has been found to be associated with the serum enzyme whose primary role is to protect LDL-C (the “bad” cholesterol) from oxidative modification (into an even “worse” cholesterol).(3) Therefore, PON1 lowers the risk of coronary heart disease by preventing oxidation of LDL-C which is involved in the initiation and progression of atherosclerosis. In addition, serum PON1 activity is reduced in diabetes mellitus (4) and familial hypercholesterolemia, diseases which are associated with accelerated atherogenesis.
The frequency of PON1 allele SNP defects vary greatly across the human population and different polymorphisms can vary as far as how they effect the production and function of the enzyme. There are clinical reports that have demonstrated that PON1 activity is reduced in patients with acute myocardial infarction, Type 2 diabetes mellitus patients with peripheral neuropathy and retinopathy. (5)
In humans, PON1 activity increases from birth to 15-25 months of age, when it seems to reach a plateau whose level is determined by the polymorphisms and the genetic background of the individual. (6) Exposure to mercury compounds will decrease liver activity of PON1. Interestinly, administration of lipopolysaccharide, which mimics gram-negative infections like Lyme disease, causes a transient decrease in serum and liver PON1 activity. (7) It also should be noted that PON1 activity can sharply decease during pregnancy and all expecting mothers should be cautioned to protect themselves from pesticide exposure.
Both cigarette smoke and alcohol has shown to inhibit PON1, though wine, due to its content of resveratrol, can increase activity. Diets high in trans-unsaturated fat content can reduce PON1 activity, but oleic acid from olive oil is associated with increased activity giving reason for the Mediterranean-type diet.
PON1 is highly susceptible to inactivation by oxidation, therefore PON1 activity is protected by the anti-oxidant polyphenols. Nutrients such as quercetin, resveratrol, turmeric, stinging nettle, astaxanthin and EGCG from green tea extract can both stabilize and raise PON1 activity. We created our Phase 2, PON1 Assist product with this in mind.  Other studies have shown that consumption of pomegranate juice which is rich in polyphenols and other antioxidants, can raise PON1 activity. (8)

NOTE: All of the above statements have not been evaluated by the Food and Drug Administration. This and any product(s) discussed are not intended to diagnose, treat, cure, or prevent any disease.

1. Mazur, A., An enzyme in animal tissue capable of hydrolyzing the phosphorus-fluorinebond of alkyl fluorophosphates., J. Biol. Chem., 1946, 164: 271-289.
2. Mackness, M. I., Arrol, S. and Durrington, P. N., Paraoxonase prevents accumulation oflipoperoxides in low-density lipoprotein, FEBS Lett, 1991, 286: 152-154.
3. Watson, A. D., Berliner, J. A., Hama, S. Y., La Du, B. N., Faull, K. F., Fogelman, A. M.and Navab, M., Protective effect of high density lipoprotein associatedparaoxonase. Inhibition of the biological activity of minimally oxidized low densitylipoprotein, J Clin Invest, 1995, 96: 2882-2891.
4. Abbott, C. A., Mackness, M. I., Kumar, S., Boulton, A. J. and Durrington, P. N., Serumparaoxonase activity, concentration, and phenotype distribution in diabetesmellitus and its relationship to serum lipids and lipoproteins, Arterioscler ThrombVasc Biol, 1995, 15: 1812-1818.
5. Ikeda, Y., Suehiro, T., Inoue, M., Nakauchi, Y., Morita, T., Arii, K., Ito, H., Kumon, Y.and Hashimoto, K., Serum paraoxonase activity and its relationship to diabeticcomplications in patients with non-insulin-dependent diabetes mellitus,Metabolism, 1998, 47: 598-602.
6. Costa, L. G. and Furlong, C. E., Paraoxonase (PON1) in Health and Disease: Basic andClinical Aspects. Kluwer Academic Publishers, Boston, USA., 2002.
7.  Feingold, K. R., Memon, R. A., Moser, A. H. and Grunfeld, C., Paraoxonase activity inthe serum and hepatic mRNA levels decrease during the acute phase response,Atherosclerosis, 1998, 139: 307-315
8. Kaplan, M., Hayek, T., Raz, A., Coleman, R., Dornfeld, L., Vaya, J. and Aviram, M.,Pomegranate juice supplementation to atherosclerotic mice reduces macrophagelipid peroxidation, cellular cholesterol accumulation and development ofatherosclerosis, J Nutr, 2001, 131: 2082-2089.