Insights on Clinically Actionable Genes

By: Wellness Wiz Jack Tips Ph.D., C.C.N.

Clinically Actionable Genes: PON1 Gene
Gene AKA:A-Esterase (Homocysteine Thiolactonase)
Significance:Homocysteine, Thiolactone, Intracellular Detoxification, MTHFR support, Heart Health, Liver Health, Kidney Health, Oxidative Stress, Inflammation, Longevity
Gene Test:Systemic Detoxification Profile
Blood Tests:Homocysteine, ALT, AST, GGT, Albumin, Creatinine GFR

PON1 Overview:

PON1’s Influence

Human health is greatly influenced by genes, but only influenced. Genes don’t directly flip the switches on or off for cellular behaviors—if that occurs, it’s a rare mutation as may have occurred when humans lost the ability to make intracellular Vitamin C. Individual epigenetic1 responses perform that job and implement Nature’s Prime Directives to: adapt, survive, perpetuate, and express the most optimal health possible.

Epigenetic Implementations

A person’s epigenetic responses transcribe the gene information into cellular metabolic proteins via a complex, interrelated gestalt based on thoughts, feelings, beliefs, stresses, environment (nature VS nurture), exposures (toxins, pathogens VS herbalomic™2 plant components), plus the actions of many other genes.

Empowered By Gene Knowledge

Knowing if a cell’s fundamental metabolic processes are supported or inhibited by a certain gene provides the clinician keen insights on how to naturally support cellular health, prevent disease, and extend longevity via actionable3  nutrients. Here, let’s examine how natural health practitioners use gene information to more responsibly and accurately determine lifestyle, dietary, and supplemental recommendations.

PON1 Gene – What It Does:

PON1’s purpose is to encode the Paraoxonase-1 protein in the liver, an enzyme that disassembles (hydrolyzes) many unwanted molecules, various toxins including the dangerous Homocysteine Thiolactone, intermediate metabolites, and cellular waste products that, unless properly processed, can result in disease.

  • Homocysteine is a sulfur compound that the body produces from methionine as a normal, natural re-methylation and transsulfuration activities.
  • Re-methylation is a process where a folate-derived (MTHF) methyl group or  Betaine, is added to homocysteine to convert it back to methionine. Vitamin B12 is required along with methionine synthase (MTHFR).
  • Transsulfuration is a process where homocysteine is converted to cystathionine  by cystathionine beta-synthase into the powerful antioxidant, glutathione, with the help of Vitamin B6.
  • Homocysteine Thiolactone is a neuro-toxic metabolite associated with epileptic seizures, Alzheimer’s, inflammation and the entire gamut of concerns regarding elevated homocysteine.

The PON1 Gene encodes a powerful enzyme that stands between health and diseases such as diabetes, kidney disease, heart and cardiovascular disease (coronary artery), diabetic retinopathy, high blood pressure, cirrhosis, macular degeneration, Alzheimer’s, neurological degeneration, autism, Parkinson’s, cancer, elevated homocysteine, chemical sensitivities, and elevated malondialdehyde (a marker of cell membrane damage via lipid peroxidation).

PON1 Helps:

  • Detoxify Organophosphates – Organophosphates include Parathion, Malathion, Chorpyrifos, Diazinon, Dimethoate, Glyphosate (RoundUp™ now permeating the global food supply), and Methamidophos. Organophosphates are a class of nerve-destroying insecticides used in:
    • Agriculture (in food )and acquired by the body from eating commercial foods
    • Pet and children medicines for fleas, lice
    • Homes for termites, ants
    • Chemical warfare by Iraq against Iran, Halabjeh, and Kurdistan
  • Protect Cell Membranes From Oxidized Fats – Dangerous molecules that lead to heart damage, artery inflammation, cell membrane deterioration, mitochondrial energy impairment, and autoimmune concerns. PON1 stands between healthy arteries and atherosclerosis/arteriosclerosis.
  • Cholesterol Balance – PON1 supports proper HDL/LDL ratios by helping hydrolyze damaged LDL and preventing oxidative damage to lipids throughout the body.
  • Heart/Cardiovascular. Higher PON1 activity helps prevent vascular disease and may reduce heart-attack and vasculitis risks.
  • Detoxify Bacterial Endotoxins – A component of gram-negative bacterial cell walls. Some forms are deathly toxic.
  • Interfere With Pathogenic Bacterial Signaling Molecules needed for quorum sensing and communications.
  • Alzheimer’s – PON1 provides protection for people with ApoE4 polymorphisms (associated with an increased risk of Alzheimer’s).
  • Neutralize Free Radicals – Reduces oxidative damage to DNA and cell membranes that can cause normal inflammation reactions.
  • Detoxify Homocysteine Thiolactone – A toxic cellular by-product of methylation that produces the amino acid methionine. Thiolactone attacks many types of proteins throughout the body causing tissue damage, inflammation, neurodegeneration, heart and artery disease.

Dr. Shayne Morris (with Drs. Sutton and Tips) developed a breakthrough nutritional supplement, Systemic Formulas’ Homocysteine-TLR, to specifically address the risks of elevated Homocysteine and the damaging impact of Homocysteine Thiolactone. Call 1-800-445-4647 for more information and to order.

Because of global environmental toxicity, the PON1 gene has come to the forefront to support human health and longevity with the relatively new life-threatening challenges of pesticides, herbicides, and the plethora of new chemicals to which humanity is now exposed.

Cellular Longevity

Optimizing PON1 expression and function has an immediate impact on cellular longevity. Clinicians can look at the Systemic Gene Report for key insights.

PON1 rs662 Risk Allele “C” – Highest PON1 activity.

Beneficial of antioxidant needs, and a dozen studies involving more than 6600 people reveal that people with the “C” allele have longer lives.

Example from Systemic Detoxification Profile:

Example from Systemic Detoxification Profile

Also, clinicians can check the PON1 rs854560.

PON1 rs854560 Risk Allele “T” – Risk of antioxidant needs.

The “T” allele has a greater risk of organophosphate-driven neurotoxicity and cardiovascular impact. This is not only evidence that pesticides such as glyphosate can cause disease and kill people (now well documented in scientific studies), it empowers people to be proactive to avoid commercial glyphosate corn, soy, and wheat products, and to supplement to support their most optimal PON1 performance.

Example from Systemic Detoxification Profile:

Example from Systemic Detoxification Profile

Longevity Factor4

So, when does Atropos (the ancient Greek Fate of Death) think about snipping someone’s lifeline? One good marker is: Do you have the PON1 (rs662) “C” allele, or the “T” allele. People with the “C” allele are more likely to hit the Centenarian mark. People with the “T” allele can take life-prolonging actions now, especially by supporting their homocysteine levels with lifestyle, nutrition, and supplementation.

Heart Disease

More than 60 studies involving 53,500 people connect the rs662 “C” allele with a 25% lower risk of infarction as well as a lower risk of cardiovascular disease. We know that heart health or disease is associated with many people’s prospects for longevity. The PON1 genes point to predisposing factors that become actionable with clinical nutrition and lifestyle advice revealed in the Systemic Gene Report.


Research demonstrates that the same pattern of the rs662 “C” versus “T” risk alleles applies to homocysteine and homocysteine-thiolactone. The “C” allele means that the person has an effective, operable ability to detoxify homocysteine-thiolactone; whereas the “T” allele means less ability to detoxify that cell-damaging molecule.  

Dr. Christy Sutton discusses this at the Systemic Gene Seminar, as well as additional insights from the PON1 rs854560 risk alleles “T” and “A” where the “T” allele is supportive of PON1 detoxification activities, and the “A” allele indicates an increased risk of cardiovascular disease. 

Looking at more than one risk allele provides broader insights on overall PON1 performance to make homocysteine-thiolactonase – the enzyme that destroys toxic homocysteine-thiolatone.


One way of thinking about the impact of simple gene info on human health and longevity is this. A truck sets out to pull a horse trailer over the mountain.  If it has an 8-cylinder engine, it’s easy-peasy to go the distance. But if the truck is running on 6-cylinders, the driver might make key decisions that allows it to go the distance—higher grade of fuel, clean oil, tuned carburetors, and don’t pick up a 300-lb hitchhiker. Now, if the truck is on 4-cyllinders, there will be more stress and strain on the engine and other components. Something’s likely to break under the stress of torque, altitude, and road grade. The 4-cylinder engine may not go the distance. 

Knowing how many of a person’s genetic “cylinders” are firing can help clinical nutritionists make good decisions on lifestyle, diet, and supplements. You can optimize the cell-supportive molecular resources that you and your patients have to work with.


These gene insights, obtained from the Systemic Gene Report, help clinicians responsibly determine which supplements are scientifically validated to impact more healthy cellular metabolic functions. The A.I. algorithm compares a gene to other genes to automatically asses a Risk Factor by looking at the greater totality of gene-factors.

In the case of the PON1 Gene, science points to the advantages of an organic, Mediterranean-type diet (organic extra-virgin olive oil), green tea catechins (EGCG), blueberries, pomegranate, quercetin, Vitamin C, Resveratrol, Folate/Methylfolate, Curcumin, berberine (richly found in goldenseal, barberry, and Oregon grape root), and antioxidant supplements.

Q. Who needs to know their PON1 Risk Alleles?
A. People who want to be proactive regarding:

  • Elevated homocysteine
  • Protection against side effects from Rx statin drugs (statins lower PON1 enzymes)
  • Liver or kidney concerns
  • Brain & Neurological concerns
  • Health and longevity optimization.

Knowledge Is Power

The Systemic Gene Test and resulting Gene Report in the hands of trained natural health professionals are powerful, clinical tools that are revolutionizing Functional Medicine and Clinical Nutrition with science-backed authority to employ supplements for more optimal health, longevity, and prevention of disease.

High Demand

Gene Testing is in high demand. Patients want to know. Early-responding clinicians are seeing a dramatic increase in their case-loads and revenue; but most importantly, gene testing provides a clinically-responsible, actionable basis for natural health advice.

What Now? Action-Item Checklist:

  • Enroll in the Systemic Gene Test Program and implement with your patients. Click Here for more info and to enroll.
  • Get your personal Gene Report. Order your DNA Test Kit at 800-445-4647.
  • Order Homocysteine-TLR – the premier homocysteine product for clinical practice. To learn more, Click Here.

1 Epigenetics – The Study of heritable changes in gene expression caused by factors (ex: DNA methylation) rather than a change in the sequence of base pairs of DNA. The activation and deactivation of genes that occur without DNA mutation (changes in DNA sequences).

2 Herbalomics – The epigenetic impact of botanical molecules on DNA expressions of health and disease. © by Shayne Morris. Reveals “actionable” nutrients based on scientific studies.

3 Actionable – Scientific validation that a decision can be made, and action taken, because there is sufficient grounds for that action. Ex: Scientific study proves the beneficial impact of herbal, nutriment supplementation regarding a gene report’s identification of gene expressions.

4 Longevity – Lescai F, Marchegiani F, Franceschi C. PON1 is a longevity gene: results of a meta-analysis. Ageing Res Rev. 2009 Oct;8(4):277-84. doi: 10.1016/j.arr.2009.04.001. Epub 2009 Apr 17.