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Health Protocols

Metabolic Detoxification

What is Metabolic Detoxification?

Metabolic detoxification, within the context of this protocol, is the pathway by which the body processes unwanted chemicals for elimination. The body metabolizes xenobiotics (foreign chemicals) and unnecessary endobiotics (endogenously produced chemicals) so they can be excreted.

Excess hormones, environmental toxicants, and prescription drugs are all cleared via the same enzymatic detoxification systems. Metabolic detoxification is therefore essential for protecting the body from environmental factors and maintaining internal homeostasis.

Natural interventions, such as B vitamins and sulforaphane, may help support detoxification pathways by promoting the activity of essential enzymes.

Note: The body is generally very effective at detoxifying itself. Providing the body with essential vitamins, minerals, and other nutrients is the best way to ensure proper detoxification. Many diets and trends that claim to “detox” the body are pushing the boundaries of scientific plausibility and may even be harmful.

How Does the Body Detoxify Itself?

The metabolic detoxification process is comprised of three essential steps:

  • Phase I—enzymatic transformation:
    • Purpose is to chemically transform compounds from lipid-soluble into more water-soluble
    • Generally carried out by cytochrome P450 (CYP) enzymes
  • Phase II—enzymatic conjugation:
    • Purpose is to further increase water solubility and decrease reactivity of phase I products
    • Generally carried out by UDP-glucuronlytransferases (UGTs), glutathione S-transferases (GSTs), and sulfotransferases (SULTs)
  • Phase III—transport:
    • Purpose is to excrete water-soluble compounds from the cell
    • Generally carried out by ATP-binding cassette (ABC) transporters

Note: Products of phase I are often more toxic than the original compounds. Phase II reactions neutralize the products to decrease their toxicity. Several factors, including dietary influences, smoking and consuming alcohol, advanced age, and certain diseases may cause phase II enzymes to become overwhelmed (leading to toxicity, such as seen in acetaminophen overdose).

How Can You Minimize Exposure to Toxins/Toxicants?

  • Choose cleaning products that are free of volatile organic compounds
  • Choose wood, tiles, or other alternatives for flooring instead of carpet
  • Use bisphenol A (BPA)-free or phthalate-free plastic containers; avoid warming food in plastic
  • Choose organic produce when possible
  • Wash fruits and vegetables before consuming or remove peel
  • Limit intake of processed foods
  • Cook foods at lower temperatures; avoid charring

What Natural Interventions May Help the Body Detoxify?

  • Vitamins. Deficiencies in vitamins A, B2, B3, B9 (folate), C, and E are linked with decreased phase I activity and can slow the metabolism of certain drugs. B vitamins are also particularly important as cofactors in phase II reactions.
  • Minerals. Deficiencies in iron, calcium, copper, zinc, magnesium, and selenium have been shown to reduce phase I enzymatic activity.
  • Methionine and cysteine. The reduced glutathione for GST conjugation requires adequate dietary sulfur-containing amino acids (methionine or cysteine) for activity.
  • Flavonoids. Several flavonoids have demonstrated mild inhibition of multiple CYPs in animal models (which can help when phase II enzymes are overloaded); these include genistein, diadzein, and equol from soy, and theaflavins from black tea.
  • Green tea extracts. Tannins from green tea can increase CYP activity in vivo, but also increase phase II activity (GST and UGT).
  • Sulforaphane. Sulforaphane, an isothiocyanate found in broccoli and other cruciferous vegetables, is among the most potent natural inducers of phase II detoxification enzymes.
  • D-limonene. D-limonene has some chemopreventive activity due to its induction of phase I and II enzymes. In rats, D-limonene has been shown to increase total CYP activity, intestinal UGT activity, and liver GST and UGT activity.
  • N-acetyl cysteine (NAC). NAC can provide sulfur for glutathione production. It is effective at reducing oxidative stress, particularly due to heavy metal toxicity.
  • Milk thistle. The milk thistle derivative silymarin promotes detoxification by several complementary mechanisms. It can act as an antioxidant to lower the liver oxidative stress associated with toxin metabolism, which conserves cellular glutathione levels.
  • Artichoke. Artichoke and other plants and vegetables can stimulate bile flow, which is essential for toxin excretion.
  • A variety of natural products have been shown in vitro or cell culture to directly increase activity of phase II enzymes; these include epigallocatechin gallate (EGCG), resveratrol, curcumin and its metabolite tetrahydrocurcumin, alpha lipoic acid, alpha tocopherol, lycopene, gingko biloba, allyl sulfides from garlic, among others.
  • Other natural interventions that may be helpful for detoxification include calcium-D-glucarate, chlorophyllin, probiotics, and derivatives of quercetin.
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