An Integrative Approach to Liver Detoxification

By Jim Paoletti, B.S. Pharmacy, FAARFM, FIACP | Director of Education, Power2Practice

A discussion of detoxification could include everything from spiritual cleansing to scientific and physiological detoxification. Detox includes Integrative methods ranging from fasting, colon cleaning and ionic food detoxification to more conventional chelation and enzymatic nutritional support.


Metabolic Detoxification

This Integrative liver detoxification protocol refers to the metabolic pathways which process unwanted chemicals for elimination, otherwise known as “Metabolic Detoxification.” The enzymatic reactions that neutralize and solubilize toxins so that the liver and kidneys can excrete them is the primary mechanism for elimination of foreign chemicals and unnecessary or excess endogenously produced substances. Metabolic detoxification reactions help protect from environmental toxins, drugs, excess hormones, vitamins and inflammatory molecules.

The rationale for detoxification is simple: We ingest and are exposed to many toxins in today’s world. Toxins can act as carcinogens or mutagens and disrupt numerous metabolic pathways, leading to a multitude of detrimental effects. In 2006, the CDC reported that the average American has 116 of 148 tested synthetic compounds in their body. Most food contains chemicals that need to be detoxified properly or they are deposited in various tissues. The increased toxic load leads to inflammation as most toxins are pro-inflammatory. A chronic state of inflammation from accumulated toxins leads to disease.


Exogenous & Endogenous Toxin Exposure 

Lifestyle choices can increase toxic burden stressing the detox capacity of the liver. These include smoking, excessive alcohol and caffeine consumption, drugs (recreational, prescription and OTC), and dietary choices of fast foods, refined foods, artificial food additives like preservatives and colors, antibiotics and growth hormone used in production of meats.


Additional environmental sources of exogenous toxins include (but are not limited to):

  • Air pollution (factories, vehicle emissions)
  • Smoke
  • Pesticides, herbicides, insecticides and fertilizers
  • Solvents (cleaning agents, gasoline, glue, paints, nail polish & remover, perfumes, etc.)
  • Plastics that have been subjected to heat
  • Artificial preservatives
  • Heavy metals
  • Non-purified water
  • Excessive alcohol or caffeine
  • Dyes
  • Chlorinated & brominated products (commercial bread products)
  • Radiation & EMFs (cell phone, Wi-Fi, cordless phones, radiology, air planes, electronic clocks). Keep phones, computers, electronic clocks, etc. at least 8 feet from bed.
  • Microwave ovens
  • Poor quality fats (canola, soy and corn oils, etc)


Endogenous toxins can add to the detoxification burden of the liver. Endogenous toxins include:

  • Bacterial, fungal and yeast overgrowth
  • Metabolic reaction byproducts like CO2 and ammonia (in excess)
  • Hormones (excess)
    • Note: excess hormones can be caused by overproduction, and/or by poor elimination (which in turn leads to more toxic burden)
  • Undigested food in the GI tract
  • Stress
    • Turns off & on genes that regulate fat storage, immune function, and hundreds of enzymes that break down fats and detoxify drugs
    • Slows gut transit which increases recirculation of estrogens and exogenous toxins


Fat Soluble Toxins Can Deposit in the Lipid Membrane & Adipose Tissue

The effects of stored toxins can be continuous and permanent if allowed to remain in the body. Toxins may be an underlying causes for chronic illness because of their effects on the gastrointestinal, cardiovascular, neurological, immune and muscular systems. Optimizing function of the metabolic detoxification processes improves the efficiency of the liver, kidney and intestines.

Liver detoxification is part of the process for the functional approach to GI health. Chronic GI complaints are the most common reason why people seek medical care. Without good functioning of the GI tract, there won’t be proper absorption and assimilation of nutrients for running detox pathways.


The pillars of GI health include digestion, elimination, microflora balance and gut integrity.

  • Digestive enzymes can be very beneficial to help patients break down complex food molecules and nutrients to be absorbed, and therefore important to the detoxification pathway.
  • Elimination refers to getting rid of toxic metabolites from the body. When toxins are removed by enhancing liver detoxification pathways, often improvement is seen in all four pillars of GI health.

As you can see, GI health affects and is dependent on proper detoxification, and visa versa.

There is more than one organ that assists in the detoxification process, as the skin helps detoxify through sweating and the kidney through urination. However, the most important organ for detoxification is the liver.


The 2 Phases of Liver Pathway Detoxification

Both culminate in elimination of the products via liver metabolism.


Phase I detoxification is enzymatic transformation. Enzymes chemically transform lipid soluble compounds into water soluble compounds. The majority of Phase I detoxification reactions are performed by the cytochrome P450 family of enzymes (CYPs). CYP enzymes are relatively non-specific and can act on numerous types of toxins. Other enzymes that contribute to Phase I detoxification include:

  • Flavin monooxygenases (FMOs), which metabolize nicotine
  • Alcohol and aldehyde dehydrogenase, which metabolize alcohol
  • MOAs (monoamine oxidases) which metabolize neurotransmitters and some antidepressant drugs

The CYP1A2 enzyme is responsible for Phase I metabolism of approximately 50% of drugs. Patients taking multiple medications can overwhelm the CYP1A2 enzyme, leading to side effects and drug-to-drug interactions.


Phase II detoxification is enzymatic conjugation. Metabolic products from phase I detoxification are more water soluble. However, they are not yet made totally suitable for elimination. These molecules may not be sufficiently water soluble for complete elimination and often are reactive molecules that if not eliminated can cause oxidative damage. Phase II enzymatic reactions make the molecules more water soluble and less reactive. Phase II enzyme activity is considered anti-carcinogenic and anti-mutagenic. The Phase I metabolism of toxins triggers the oxidative stress response of activation of nuclear factor erythroid-derived 2 (Nrf2), the protein that controls the production of most Phase II enzymes. Nrf2 also activates synthesis of the detoxification molecules superoxide dismutase (SOD) and glutathione, and activates the initial processes in heavy metal detoxification.


Phase II enzymes include:

  • Glutathione S-transferases (GSTs) that catalyze transfer of glutathione to Phase I metabolites including sex steroids, thyroid hormones, fat-soluble vitamins, bile acids, bilirubin, and prostaglandins. GSTs also have antioxidant properties and detoxify free radicals and oxidized lipids or DNA. Glutathione conjugates are excreted via the bile or delivered to the kidney for further processing and elimination.
  • Methyltransferase enzymes. Catechol 0-methyltransferase (COMT) eliminates catecholamine neurotransmitters.
  • Sulfotransferases (SULTs) that attach sulfate groups in Phase I and II reactions. SULTs metabolize drugs, sex steroids, thyroid, adrenal hormones, serotonin, ascorbate and Vitamin D). Note, unlike other Phase II enzymes, SULTs can convert some pro-carcinogens into more reactive intermediates which may act as chemical carcinogens and mutagens.
  • UDP-glucuronyltransferases (UGTs) which attach glucuronic acid to toxins in the process referred to as glucuronidation. Drugs, xenobiotics and many environmental toxins (including bisphenol A from plastics and benzopyrene from cooked meats) are metabolized by UGTs.
  • The amino acid conjugating enzymes attach amino acids to xenobiotics and food preservatives like benzoic acid


The final step in detoxification is transport. Transporters actively pump water soluble Phase II metabolites out of cells of the liver, kidney and intestines. These transporters are proteins referred to as ABC transporters (for the ATP binding Cassette) because they require energy from ATP.


Caution: Phase I reactions potentially produce more reactive and toxic molecules, therefore inducing Phase I reactions when Phase II enzymes are not functioning at a rate to rapidly neutralize the Phase I products can increase health risks. Factors that increase Phase I reactions include nicotine and alcohol.


Signs and Symptoms of Toxin Buildup Include:

  • Headaches
  • Muscle aches and pains
  • Fatigue
  • Asthma
  • Allergies
  • Skin disorders, including acne and rosacea
  • Unexplained weight gain and inability to lose weight
  • High blood pressure
  • Fatty yellowish lumps around eyes
  • Abdominal bloating
  • Excessive abdominal fat
  • Pain or discomfort over the liver
  • Trouble digesting fatty foods
  • Acid reflux and heartburn
  • Dark spots on skin
  • Over-heating of the body and excessive perspiration
  • Chronic Infections
  • Mood swings
  • Poor mental function
  • Lowered stress tolerance
  • Decreased libido
  • Infertility


The Goals of a Liver Detox Are:

  • Minimize exposure to and consumption of all toxins.
  • Increase intake of nutrients required for detoxification by diet and/or supplementations.
  • Optimize bowel function and bile flow to help elimination.
  • Increase fruits and vegetables to increase alkalinity along with adequate purified water to increase urinary elimination.


How to Detox the Liver:

The detoxification process can be as simple as avoiding the toxins the body is exposed to for a certain period of time, usually 7 to 30 days. Add to that good, healthy eating.

Most often, the diet component is combined with nutritional support for Phase I and Phase II enzyme reactions, again for 7-30 days. Additional detox measures can be incorporated, such as daily sweating. Break a good sweat daily and consume plenty of purified water during and after the exercise or sauna treatment. Examples of other additional measure would be chelation therapy for heavy metal detoxification, or removal of mercury fillings by a qualified trained dentist.


The patient starts the process of detox by reducing the toxic load:

  • Avoid exposure to environmental toxins.
  • Reduce exposure from toxins in food and drink.
  • A liver detox diet emphasizes organic natural whole foods in order to avoid all pesticides, antibiotics, artificial additives, high fructose corn syrup, hormones, etc. It also should contain alkaline foods like potassium-rich fruits and vegetables, while avoiding acid-inducing foods like refined carbohydrates.
  • Increase purified water intake to the half of the patient’s weight in pounds in ounces (150 pounds equals 75 ounces of water).
  • Avoid common allergies to decrease risk of inflammation (gluten, daily, soy and egg).


Detox kits: Most nutritional companies have kits available for a 1 week to a 1 month detox program. The kits contained detailed information on the detox diet, and the supplements that support detoxification mechanisms. The kit may also contain a nutritional beverage mix. Some of the nutritional supplements you may see used for detox support include milk thistle, artichoke leaf extract, pomegranate extract, green tea extract, turmeric, glucosinolates, sulphoraphane, n-acetylcysteine, MSM, alpha-lipoic acid, dandelion, selenium, methionine, and certain amino acids. Phase 1 detoxification is supported by vitamins B2, B3, B6, B12, and C, folic acid, niacin, magnesium, copper, zinc, and flavonoids.


Lastly, I would caution against detox programs that include fasting, with or without a “cleanse.” These programs are a type of starvation, which slows down metabolism. A daily laxative for cleansing can cause dehydration, deplete electrolytes, and impair normal bowel function.


If a patient appears to be fairly toxic, or someone with high exposure to toxins (hairdresser, lawn service personnel, etc.)… my advice is to do a detox diet only for at least 7 days before adding nutritional support. Toxins released from the fat cells into the bloodstream when metabolism is increased can cause temporary unpleasant symptoms including headache, chills, fatigue, dizziness, irritability, body odor, foul smelling stools, body aches and general flu-like symptoms. These symptoms can persist several days in some individuals, so if in doubt, go more slowly with the detox. Avoid toxins and follow a detox diet for 7-10 days before initiating nutritional supplementation to support liver metabolism.


Jim Paoletti - Director of Education - Power2PracticeJim Paoletti, BS Pharmacy, FAARFM, FIACP, is the Director of Education at Power2Practice and a Clinical Consultant with over 30 years of experience creating and using bio-identical hormone therapies in both retail pharmacy and clinical practice.

Jim is a Diplomat in Functional Medicine in addition to being a former faculty member for the Fellowship of Functional Medicine.

At Power2Practice, he applies his wealth of knowledge and experience by hosting live webinars and creating useful content, such as blogs, podcasts and clinical support tools.