Updated 10/8/23; Originally posted 4/24/22

A great many toxins are fat soluble. As the toxins are liberated from your fat cells, they are converted to “active metabolites”. In this state they are free to roam around the body and cause trouble because they are looking for someone to “be active” with. Your lymph system guides these toxins into your blood stream so that your liver can do one of its primary jobs in life – help your body get rid of toxins!

Importance of the Liver’s Phase 2 Detox

The first step of the liver is to convert the toxin from fat soluble to water soluble (Phase 1). The second step the liver takes is uses chemistry(!) to conjugate or “put a handle” on the water soluble toxin. Once the “handle” is attached the bile and the kidneys can “grab the handle” and throw the toxin out of your body via Phase 3 (poop and pee). When no handle gets attached, the toxin is slippery and evades your captors.

liver of a woman
Your liver is a crucial detox organ

Many recent studies into cancer, Parkinson’s, immune disorders, lupus, and other diseases indicate a direct causal relationship with poor Phase 2 detoxification. Poor Phase 2 detoxification is also implicated in migraines, depression, autism, chemical sensitivities, insomnia, hot flashes, hangovers, asthma, chronic fatigue, neurodegeneration, liver cancer, chronic joint issues, and the list goes on!

How Does Phase 2 Liver Detox Work?

There are 6 types of “handles” or conjugations that can be used depending on the available ingredients, your genetic predisposition to favor (or not!) certain “handles” or pathways, and your ability break down and recycle the ingredients to be reused. Required ingredients include vitamins, minerals, antioxidants, and amino acids. Which pathways are most important for you depend on which toxins you are dealing with as some have only 1 pathway that works. Which pathways you need to actively support depends also on your personal genes and how they are expressed due to your wellness lifestyle.

Sulfation Pathway

Requires: the presence of inorganic sulfur and properly active SULT enzymes

Sulfate molecule

Commonly used for: endo and exotoxins – it is the primary way our bodies recycle hormones and neurotransmitters:

  • break down of excess steroid hormones (estrogen, progesterone, DHEA, Melatonin),
  • break down of excess thyroid hormones
  • break down of excess neurotransmitters (epinephrine, norepinephrine, dopamine)
  • exotoxins like BPA (from plastics), triclosan (antibacterial found in cleaning and personal care products), and BHT (food additive)
  • xenoestrogens (chemicals that mimic estrogen)
  • endotoxins from intestinal bacteria

Support for optimal sulfation:

  • Epsom salts foot bath or whole body bath (magnesium sulfate)
  • Eat sulfur rich vegetables from the allium and cruciferous families- onion, garlic, leek, broccoli, cabbage, kale, brussel sprouts, and radishes
  • Eat eggs and meat
  • Supplement with NAC or glutathione
  • Get sunshine on your skin to make cholesterol sulfate and vitamin D sulfate
  • The mineral Molybdenum helps convert sulfites (in wine and more) to sulfates that are usable
  • Taurine which you can get with your magnesium when you take Magnesium Breakthrough
  • Healthy Pee! Most end products are passed out via your urine

Causes of suboptimal sulfation:

  • Low protein diet
  • Low sulfur intake
  • Low magnesium
  • Issues with the effectiveness of the SULT family of enzymes
  • High toxic load

Glucuronidation Pathway

Requires: presence of glucuronic acids (comes from glucose) and properly active UGT enzymes

Glucose molecule

Commonly used for:

  • Breakdown of sex hormones (testosterone, estrogen, DHEA)and thyroid hormones
  • Bilirubin (a by product of red blood cell recycling – makes the yellow/brown color of a bruise)
  • Some mold mycotoxins (mold chemical warfare materials)
  • Medications like NSAIDs, Tylenol, Codeine, and Morphine

Support for optimal glucuronidation:

  • Supplements that encourage UGT enzymes (resveratrol, curcumin, d-limonene, quercetin)
  • Supplements that encourage low levels of the enzyme beta-glucuronidase in the gut (high levels encourage reabsorption rather than recycling) like calcium d-glucurate and probiotics/prebiotic
  • Optimal magnesium and B vitamin levels (remember these are water soluble)
  • Drink dandelion, rooibos, or rosemary tea
  • Astaxanthin (I get mine via my Omega 3 Supplement)
  • Healthy poop! Most end products are excreted through your bowels

Glutathione Conjugation Pathway

Requires: Presence of glutathione which is known as the master antioxidant (and is crucial for Phase 1 Detox as well) and a properly active Glutathione transferase enzyme

Glutathione molecule

Commonly used for: almost all the environmental toxins and carcinogens we are exposed to daily:

  • Pesticides and herbicides in the air (newly sprayed) and in your food
  • Heavy metals (mercury, lead, cadmium, arsenic)
  • Most mold mycotoxins (mold’s protective chemical warfare)
  • Medications like Tylenol and tetracycline
  • Alcohol

Support for optimal glutathione conjugation:

  • You need glutathione! You make it when needed from the precursor molecule NAC and it breaks down into homocysteine.
  • Plenty of cysteine, glutamine, and glycine (from meat and collagen) in your diet as these 3 amino acids combine to create glutathione
  • Plenty of Vitamin C, Vitamin E, and Alpha Lipoic Acid to help you recycle your glutathione for reuse
  • High Omega 3 fatty acids levels in your body keep your glutathione level high too – check yours via an at home Omega 3 Index Blood Test and supplement!
  • Plenty of Selenium to activate the enzyme that controls glutathione usage

Methylation Pathway

Requires: Vitamin B12 and B9 (folate) and properly active COMT and SAM enzymes

Methyl molecule

Commonly used for: many biochemical processes including detoxification of:

  • Break down of excess estrogen
  • Break down of neurotransmitters (serotonin, melatonin, epinephrine, norepinephrine, dopamine)
  • Histamine and tyramine
  • Phenols like salicylic acid—aspirin, cannabinoids, estradiol, and BPA
  • Arsenic
  • Phenols found in BoTox, petroleum, plastics, and vaccine preservatives
  • Carcinogenic aromatic amines found in cigarette smoke, dyes, adhesives, perfume, pharmaceuticals, pesticides, explosives, diesel exhaust, combustion of wood chips, and grilled meats and fish

Support for optimal methylation:

  • Avoidance of inhibitors like birth control pills, antibiotics, proton pump inhibitors (PPIs), sucrose, and nitrous oxide
  • Poor gut health
  • Supplement with active (methylated) forms of Vitamin B9 and Vitamin B12 (I get mine from BioActive Complete B-Complex)
  • Eat or supplement with minerals that support the creation of methyl groups: B6, B2, magnesium, zinc, and choline
  • Beware elevated homocysteine levels in your blood that accompanies poor methylation

Note: There is a lot of buzz about the genetic variations of the MTHFR genes that relate to this pathway. Remember that your wellness lifestyle affects how those genes are used or not!

Acetylation Pathway

Requires: available acetyl co-A molecules and a properly active NAT2 enzyme (most important liver enzyme)

Acetyl molecule

Commonly used for: throughout the body as part of the mitochondrial action to generate energy (ATP) and also in the liver to detox from:

  • Caffeine
  • Tobacco
  • Histamine
  • Serotinin
  • Salicylic acid found in foods, medications,
  • Carcinogenic aromatic amines found in smoke and car exhaust (and more!)

Support for acetylation:

  • The most important factor is the optimal functioning of your NAT2 genes
  • Minerals and vitamins that support this pathway include molybdenum, iron, Vitamins B1, B2, B3, B5, and Vitamin C

Amino Acid Conjugation Pathway

Requires: Presence of the amino acids primarily glycine (not the pesticide glyphosate!), taurine, glutamine, arginine, and ornithine and properly active GLYAT enzymes

Glycine molecule

Commonly used for:

  • Aspirin
  • Alka-seltzer
  • Non-steroid anti-inflammatory medications
  • Foods that supply salicylates
  • Food dyes – particularly red and yellow
  • Toluene found in pain thinner, nail polish, ink, and stain removers
  • Sodium Benzoate serving as a preservative in food, personal care products, and medications
  • Some mold mycotoxins

Support for Amino Acid Conjugation:

  • An acidic body suppresses this pathway, an alkaline body activates this pathway
  • Low intake of salicylates
  • Low intake of the pesticide glyphosate
  • High intake of amino acids (protein!) including collagen, meat, and eggs
  • Co-factor minerals and vitamins including Vitamin B9 (folate), manganese, and Vitamins B2 and B6

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