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Detoxification and the liver

Symptoms Of Toxic Build Up

Headaches • Muscle aches and pains
• Fatigue • Asthma
• Allergies • Skin disorders
• Chronic infections • Neurological toxicity
• Endocrine toxicity -

Neurological toxicit

  • Affects cognition
  • Mood
  • Neurological function

Endocrine toxicity

• Affects reproduction • Menstruation
• Libido • Metabolic rate
• Stress tolerance • Glucose regulation

Toxic Exposure

According to the EPA, more than 4 billion pounds of chemicals were released into the ground in the year 2000, threatening the natural ground water sources.
The average American unknowingly eats about 124 pounds of additives a year.
Each year over 2.5 billion pounds of pesticides are dumped on crop lands, forests, lawns, and fields.

Exposure to toxins is increased by:

• Eating a diet high in processed foods and fat • Drinking tap water
• Excessive consumption of caffeine containing beverages • Excessive alcohol consumption
• Tobacco use • Chronic use of medication
• Lack of exercise • Liver dysfunction
• Kidney problems • Intestinal dysfunction
• Occupational exposure • Using pesticides, paint, and other toxic substances without adequate protective gear
• Living or working near areas of high vehicle traffic or industrial plants -

The Detoxification Process

  • Detoxification is a process by which the body transforms toxins and medications into harmless molecules that can be eliminated.
  • It takes place primarily in the liver and to a smaller degree in other tissues.

Detoxification Is Accomplished In Two Phases

Phase I-Certain enzymes change toxins into intermediate compounds

Phase II-Other enzymes convert the intermediate compounds created in Phase I into harmless molecules that are eliminated by the body.

Phase I

Enzymes in the cytochrome P-450 system use oxygen to modify toxic compounds, medications, and steroid hormones.

This is the first line of defense for the detoxification of all environmental toxins, medications, supplements including vitamins, as well as many waste products that the body produces.

Occurs in the liver

NB. If there is increased Phase I clearance without increased Phase II clearance, this can lead to the build up of intermediates that may be more toxic than the original substance. Decreased Phase I clearance will cause toxic accumulation in the body. Adverse drug reactions can be due to decreased clearance of Phase I. Within the genetic makeup are variations called single nucleotide polymorphisms, (SNPs). SNPs code for a particular enzyme that can increase or decrease the activity of that enzyme. Therefore, SNPs may increase or decrease the clearance rate. Both can be toxic.

Phase I

In this phase large water-soluble molecules are added to toxins, usually at the reactive site formed by Phase I reactions.

After Phase I modifications, the body is able to eliminate the transformed toxins in the urine or the feces.

Phase I Detoxification Requires

• Niacin • Magnesium
• Copper • Zinc
• Vitamin C • Vitamins B2, B3, B6, B12
• Folic acid • Flavonoids

Phase II Detoxification Has 6 Phases

• Glutathione conjugation • Amino acid conjugation
• Methylation • Sulfation
• Acetylation • Glucuronidation

Glutathione Conjugation

Glutathione is the strongest antioxidant that the body makes
-Requires glutathione and B6

Amino Acid Conjugation

-Requires glycine, taurine, and glutamine

Methylation

-Needed for many reactions in the body

-Requires folic acid, choline, methionine, trimethylglycine(TMG), s-adenosylmethionine (SAMe)

Sulfation

-Required cysteine or NAC (N-acetyl cysteine), methionine, and molybdenum

Acetylation

-Requires acetyl CoA

Glucuronidation

-Requires glucuronic acid

Detoxification Testing

-Detoxification of Phase I and Phase II can be measured.

-SNPs can be evaluated.

-For example, CYP3A4, affects an enzyme that the body uses to detoxify over 50% of all drugs. (These medications include many antidepressants, steroid hormones, and cholesterol lowering medications.)

Detoxification

-Adverse reactions to prescription drugs have been ranked as the fourth to the sixth leading cause of death in the United States.

-Each year about 100,000 Americans die from adverse reactions to medications.

-This is more than double the number killed in motor vehicle accidents.

-Annual hospital costs from these reactions have been estimated to be between $1 to $4 billion.

Summary of Phase I and Phase II

-Phase I and Phase II enzymes are the engines that run the detoxification process.

-They are fueled by vitamins, minerals, and other key food components.

-Therefore, if the patient is undernourished or lacks key vitamins or nutrients, they may not be able to detoxify.

Reference

The Importance of Detoxification, Advanced Nutritional Publications, Inc., 2002.
Lazarou, J., et al., "Incidence of adverse drug reaction in hospitalized patients," JAMA 1998; 279(15):1200-1205.

 
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