Detox Program


3 Phases of Liver Detox

INFLAMMATION TURNS DOWN DETOXIFICATION

is most commonly diagnosed by a routine liver function test drawn from your blood. The alanine aminotransferase (ALT) is a specific marker for liver inflammation and is typically elevated in individuals with a fatty liver.

How Urea is created: Ammonia from the breakdown of protein, is combined with CO2. Blood urea nitrogen (BUN) or serum urea nitrogen is the end product of the hepatic detoxification of ammonia. It is this parameter that is sometimes also used to assess liver function. Urea nitrogen concentration in blood may decrease with impaired conversion of ammonia to urea by the liver. High BUN Symptoms: Needing to urinate (pee) more often or less often than usual

  • Itching
  • Fatigue
  • Swelling in your legs, feet, or ankles
  • Muscle cramps
  • Trouble sleeping

Ammonia detoxification predominantly takes place in the liver. When the liver fails, the homeostasis is altered and muscle tissue becomes the main alternative organ for at least temporary detoxification of ammonia. BCAA are believed to support this muscle ammonia detoxification and the ammonia lowering effect of BCAA has been intensely investigated. In this review the effect of BCAA on muscle ammonia metabolism and the protein sparing and anabolic effects of BCAA are discussed. 

Ammonia (NH3) is produced as a byproduct of amino acid catabolism. Bacteria in the small intestines produce ammonia from glutamine, and urease-containing bacteria in the colon produce ammonia from breakdown of proteins and urea. Ammonia is taken up from portal blood by hepatocytes and converted to urea through the Krebs-Henseleit cycle (which is also less formally but more aptly known as the “urea cycle”).

Hypomagnesium can lead to low potassium contributes to hyperammonemia by decreasing ammonia excretion. 

Liver disorders may increase ammonia, which is transported to the brain, skeletal muscle, and kidneys for elimination.  

Massive sequestration of parasites in brain microvasculature increases brain ammonia levels and thereby causing ammonia toxicity (middle and left columns). Some additional effects of the malaria infection including inflammation and disrupted BBB further enhance this toxicity (right column).

How important is detoxification?

3 Phases of Phases of Detox

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Milk Thistle, herbs

Phase 1 Detoxification Pathway:

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Toxins are harbored in the body in fat and as such can be difficult to remove from the body. The body in it’s wisdom has coated these harmful toxins in fat globules so that they would cause no harm to other more sensitive tissues, think of a razor blade trapped in a wax ball. In phase one the liver releases these toxins from the fat cells. An example of the phase one pathway is the Cytochrome P-450 mixed-function oxidase enzymes. This pathway converts a toxic chemical into a less harmful chemical.  This is achieved by various chemical reactions (such as oxidation and reduction), and during this process, free radicals are produced, which, if excessive, can damage the liver cells.  

However, pesticides and other toxic manmade chemicals can disrupt the P-450 enzyme system.

 Antioxidants reduce the damage caused by these free radicals.  If antioxidants are lacking, toxic chemicals become far more dangerous. The best antioxidants to take daily to support your Phase 1 detoxification pathways are antioxidants made from whole foods.  Single vitamins such as Vitamin C or E are not effective as antioxidants, or as true vitamin complexes.  With all our present scientific knowledge we cannot duplicate vitamins in labs.  For example, if you buy Vitamin C as a supplement, you are most likely buying ascorbic acid only.  The complex Vitamin C found in fruits and vegetables is made of seven parts (ascorbic acid, flavonoids, polyphenols, catechin, rutin, and several enzymes) and ascorbic acid is only one of these parts (the outer shell of the vitamin).  Your body requires the full Vitamin C complex found in real foods.  Ascorbic acid alone cannot support Phase 1 detoxification pathway.

Whole food antioxidants are wheat sprouts, red algae and blue green algae.  From the wheat sprouts you are getting a combination of powerful metabolic enzymes (superoxide dismutase – SOD and catalase).  From the red algae, you are getting phytochemicals, carotenoids, and different vitamins.  From the blue green algae, you are getting the different minerals that act as co-factors to the different antioxidants.  These three foods have abundant antioxidant metabolic enzymes, vitamins and their minerals co-factors.

Phase Two Detoxification Pathway: conjugation pathway

Phase 2 of detoxification involves the use of the conjugation process and pathway. Conjugation is the process of a liver cell combining a transfer molecule to a toxic substance. The liver uses sulfur, glycine, cysteine and combines them to toxins making them less harmful and water soluble. These water-soluble components can now be excreted through bile and urine. whereby the liver cells add another substance (eg. cysteine, glycine or a sulfur molecule) to a toxic chemical to render it less harmful.  This makes the toxin water-soluble, so it can then be excreted from the body via watery fluids such as bile or urine.

Through conjugation, the liver is able to turn drugs, hormones and various toxins into excretable substances.  

For efficient phase two detoxification, the liver cells require sulphur-containing amino acids such as taurine and cysteine.  

The nutrients glycine, glutamine, choline and inositol are also required for efficient phase two detoxification.

Foods that have an essential and non-essential amino acid profile similar to our daily needs are excellent foods to support phase 2 detoxification pathway.  Blue green algae, bee pollen and eggs are such foods.  Sulphur compounds that can enhance phase two detoxification are found in cruciferous vegetables (e.g. broccoli, cabbage, Brussels sprouts, and cauliflower), raw garlic, onions, leeks and shallots.

 

Toxic Overload

If the phase one and two detoxification pathways become overloaded, there will be a buildup of toxins in the body.  The body encases these dangerous and oftentimes carcinogenic toxins inside fatty globules in an effort to nullify the effects. For example, think of toxins like a razor blades and the body covers in a waxy ball as protection. Once wrapped up, these offensive toxins are then cordoned off to be parked in the fatty areas of the body, such as your belly. The brain and the endocrine (hormonal) glands are fatty organs and are common sites for fat-soluble toxins to accumulate. This may result in symptoms of brain dysfunction and hormonal imbalances, such as infertility, breast pain, menstrual disturbances, adrenal gland exhaustion and early menopause.  Many of these chemicals (e.g. pesticides, petrochemicals) are carcinogenic and have been implicated in the rising incidence of many cancers.

 A recent study found the control of estrogen hormones in women was linked to the liver detoxification pathways.  Estrogen is synthesized principally in the ovaries of women, but it is detoxified and eliminated in the body through the various enzymes produced in the liver for detoxification.  The toxic effects of estrogen, therefore, can result not just as an accumulation of excessive production of estrogen from the ovaries or from the consumption of estrogen-containing medications, but also from the poor expression of detoxification enzymes in the liver.  Estrogen hormones were better metabolized and regulated by women in this study whose livers expressed proper detoxification enzyme activity, and this characteristic could be linked to diet.  Women who consume a nutrient-deprived diet that is low in B vitamins, trace minerals and antioxidants may have much more difficulty metabolizing estrogen hormones.  As a consequence, they may be at increased risk of hormone-related health problems, such as fibrocystic disease of the breast, premenstrual tension or even estrogen-induced cancer.

When liver detoxification backs up, as in the case of excessive acute toxicity or chronic toxic burden, these toxic nasties spill back into the blood stream unprocessed.  The next line of defense is the immune system. Liver overload forces or stimulates your immune system to produce inflammatory chemicals and antibodies.  If you frequently deal with swollen glands, infections, fatigue, fibromyalgia or any list of autoimmune diseases.  

 Immune dysfunction is common in the chemically overloaded environment we live in today and is exacerbated by nutritional deficiencies inherent in processed and high-fat diets.  Suppressive drugs are often used to treat symptoms of immune dysfunction.  Rarely does anyone think about the liver detoxification pathways.  Indeed, the simplest and most effective way to cleanse the blood stream and thus take the load off the immune system is to improve the liver detoxification function.


The Basics of Detoxification

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Proper nutrition supports the body’s detoxification systems.

Whether out for a run, grilling your favorite meats on a hot summer day, or spring cleaning the house, our bodies are exposed to millions of chemicals considered “toxins”. These toxins in our environment (exotoxins) and that our bodies produce (endotoxins) have the ability to disrupt the essential biological structures needed for the body to function such as DNA, cellular membranes, and protein. Repeated exposure to various toxins can contribute to adverse health effects in the short-term such as headaches, nausea, and fatigue; and in the long-term can contribute to weight gain and chronic health outcomes.

Detoxification is essential for ridding the body of toxins and preventing their “health robbing” effects. Although all cells have the ability to detoxify toxins, the most important organ for detoxification is the liver–known as the body’s filter and purification system.

Fat Cells House Toxins

Toxins enter the liver as either water- or fat-soluble molecules.  Water-soluble toxins are rather easily metabolized and excreted into the urine. In contrast, fat-soluble toxins can be stored in fat cells where they are protected from the body’s detoxification systems.

Excess fat stores, especially organ-bathing visceral fat, are linked to several diseases such as diabetes, cardiovascular disease, and metabolic dysfunction. The addition of toxin exposure to an overweight or obese individual may only serve to increase these risks (1).

Three Phases of Detoxification

There are three phases of detoxification (2). In the first step, the toxin is metabolized by phase I detoxifying enzymes resulting in an intermediary metabolite. Although there are several phase I enzymes, the most abundant and important are the cytochrome P-450s (P-450s).

During detoxification, P-450s perform two functions: 1) they make toxins more water-soluble, and 2) they convert the toxin into a molecule usually less toxic and, therefore, less reactive towards our DNA, proteins, etc. (Interestingly, sometimes this reaction converts a less toxic molecule into a more toxic molecule, which is where phase II detoxification steps in.) The result is a more water-soluble, less toxic molecule easily transported into the blood, through our kidneys, and out into the urine for elimination.

After undergoing phase I detoxification many toxins are then subject to phase II detoxification. At its most basic level, phase II enzymes place a water-soluble small molecule onto the toxin.

One of the most important phase II detoxifying enzymes is known as glutathione (GSH) transferase. As the name implies, the GSH transferases transfer a GSH molecule onto the toxin. Like phase I detoxification, this step also serves to make the toxin water-soluble and less toxic to the body.

Besides GSH, the body uses several other molecules to bind to the toxin and increase its solubility including sulfates, amino acids, and glucuronic acid. The use of these water-soluble small molecules makes sense considering that our cells have a surplus of these molecules inside or outside the cell. However, if we’re exposed to excessive amounts of toxins they could rapidly deplete our GSH levels resulting in too little GSH to do what it does best, which is to protect against free radicals and detoxify toxins.

Finally, phase III of detoxification involves the elimination of toxins from cells. In this step, the products of phase I and II reactions are transported out of cells and into the bloodstream for elimination.

Phases of Detoxification

Proper Nutrition Essential for Detoxification

To ensure optimal functioning of our detoxification systems it is essential to have an adequate dietary intake of vitamins (B vitamins, vitamins C, and E), minerals (selenium, zinc, copper), and other bioactive nutrients such as coenzyme Q10 and polyphenols. These nutrients bolster our detoxification defenses either through their roles in phases I, II or III of detoxification or by providing antioxidant support (3). Nutritional support is essential in the detoxification process because some toxins are produced as the result of free radicals. Additionally, nutritional support is needed to counteract the oxidative damage caused by toxins.

Plant botanicals including ashwagandha, aloe vera, and turmeric (Cleanse for Life), milk thistle (Product B), resveratrol, and other antioxidant vitamins and botanicals (Ageless Essential Daily Pak) have all been shown to improve detoxification. Beyond these micronutrients, the detoxification system also needs an adequate source of the amino acid cysteine, the sulfur-containing amino acid essential for GSH production. Luckily, cysteine is abundant in whey protein found in IsaLean Shakes,Bars, and Soups.

Calorie Restriction and Intermittent Fasting Stimulate Detoxification

Although not yet extensively examined in humans, subjecting animals to calorie restriction (CR) or intermittent fasting (IF) has also been shown to increase efficiency of detoxification pathways. The precise mechanisms responsible for the benefits of CR or IF on detoxification are unclear, but it’s thought that these two cleansing protocols “turn on” genes that increase synthesis of our detoxification enzymes within the phase I, II or III pathways.

Additionally, the reduction of fat mass—the primary target for toxin storage—stimulates the release of toxins into the circulation. Once in the bloodstream toxins are more easily metabolized and excreted from the body. When the body has the additional nutritional support of amino acids, vitamins, polyphenols, and other bioactive ingredients, the detoxification enzymes can perform at peak function.

The Isagenix system ingeniously incorporates both intermittent fasting on Cleanse Days and calorie restriction on Shake Days to help you burn fat and stimulate the release of fat-stored toxins. The polyphenol-rich nutrients and plant extracts found in Cleanse For Life provide plant-based antioxidants (4-7) that support the detoxification enzymes responsible for toxin elimination. Also, the whey protein in IsaLean Shake supplies essential amino acids such as cysteine that can boost GSH production (8,9) and facilitate toxin removal.

References:

1.    Holtcamp W. Obesogens: an environmental link to obesity. Environ Health Perspect 2012;120:a62-a68.

2.    Liska DJ. The detoxification enzyme systems. Altern Med Rev 1998;3:187-98.

3.    Yang YM, Noh K, Han CY, Kim SG. Transactivation of genes encoding for phase II enzymes and phase III transporters by phytochemical antioxidants. Molecules 2010;15:6332-48.

4.    Vinson JA, Al KH, Andreoli L. Effect of Aloe vera preparations on the human bioavailability of vitamins C and E. Phytomedicine 2005;12:760-5.

5.    Kim BH, Hong SS, Kwon SW et al. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages. J Pharmacol Exp Ther 2008;327:393-401.

6.    Ahmad MK, Mahdi AA, Shukla KK et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril 2010;94:989-96.

7.    Krikorian R, Shidler MD, Nash TA et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem 2010;58:3996-4000.

8.    Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med 1991;14:296-309.

9.    Sekhar RV, Patel SG, Guthikonda AP et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011;94:847-53.

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