In this Page, I will first introduce the subject (Section A) and thereafter, go into toxicity exposure (Section B) and follow-up with an overview of the body’s detox system (Section C)and then conclude with an analysis of the three different metabolic detox phases (Section D). For detox enhancement techniques, see this other Page-document.
Detoxification(“detox”) has been used to describe practices and protocolsthat embrace both complementary (fasting, colonic cleaning and more) and conventional (chelation or antitoxin therapy) schools of medical thought, as well as some that push the boundaries of scientific plausibility (such as foot pad and ionic foot detoxification).
In the context of human biochemistry, detoxification has been described as a specific metabolic pathway, active throughout the human body, that processes unwanted chemicals for elimination. This metabolic pathway involves a series ofenzymatic reactions that neutralize and solubilize toxins, and thereafter,transport them to secretory organs(ie, the liver or kidneys), so that they can be excreted from the body. This type of detoxification is sometimes called xenobiotic metabolism, because it is the primary mechanism for ridding the body of xenobiotics (foreign chemicals). There is also another type of detox system calledendobiotics(endogenously-produced chemicals).
Excess hormones, vitamins, inflammatory molecules, and signaling compounds, amongst others, are typically eliminated from the body by thesame enzymatic detoxification systemsthat protect the body from environmental toxins, or clear prescription drugs from circulation. Metabolic detoxification reactions, therefore, are not only important for protection from the environment, butcentral to homeostatic balance of the body.
Poisons: Bio-toxins, Micro-toxins and Chemo-Toxicant Exposure
Toxins are poisonous compounds. This notion is usually pertains to toxins from living organisms. The term “bio-toxin” is used to emphasize the biological origin of these compounds. Man-made chemical compounds with toxic potential are usually called toxicants. The H.M. Institute prefers to concept of chemo-toxicants. But the mainstream central distinction is between toxins of biological orgin and toxicants of synthetic origin. Both these poisons can exert their detrimental effects on health in a number of ways. Some broadly act as mutagens or carcinogens(causing DNA damage or mutations, which can lead to cancer), others can disrupt specific metabolic pathways, which can lead to dysfunction of particular biological systems such as the nervous system, liver, the kidneys or immune system.
Food intake is a major source of both toxin and toxicant exposure. Toxins can find their way into the diet by several routes, notably contamination by microorganisms, man-made toxicants (including pesticides, residues from food processing, prescription drugs and industrial wastes), or less frequently, contamination by toxins from other “non-food” plant sources. (1, 2) Some of the toxic heavy metals (lead, mercury, cadmium, chromium), while not “man-made,” have been released from the crust or via volcanoes (ie for mercury) and then redistributed into the environment at potentially dangerous levels. These chemicals can find their way into the diet as well.Microbial toxins, secreted bybacteria and fungi, can be ingested along with contaminated or improperly prepared food.
Even the method of food preparation via heat and otherwise has the potential for converting naturally-occurring food constituents into toxins. (3). For instance, high temperatures can convert nitrogen-containing compounds in meats, coffee and cereal products into the potent mutagens benzopyrene and acrylamide,respectively. Smoked fish, including wild smoked salmon, and many cheeses, especially the processed cheese, can contain precursors to toxins called N-nitroso compounds (NOCs), which become mutagenic when metabolized by colonic bacteria.
Outside of the diet, respiratory exposure to volatile organic compounds (VOCs)is a common risk which has been associated with several adverse health effects, including but not limited to kidney damage, immunological problems, hormonal imbalances, blood disorders, and increased rates of asthma and bronchitis. (4)
One of the greatest sources of non-dietary toxicant exposure is the air in the home, that which can lead to wyat is called sick building syndrome. (5) Building materials (such as floor and wall coverings, particle board, adhesives, and paints) can “off-gas” releasing multiple toxicants that can be detected in humans. (6) For example, a toxic benzene derivative commonly used in disinfectants and deodorizerswas detected in 98% of adults in the Environmental Protection Agency’s (EPA) “TEAM” study. (7) In another EPA study, three additional toxic solvents were present in 100 percent of human tissue samples tested across the country. (8) And to make matters worse, I’ve heard recently over the radio that the CDC now recognizes that all American babies born in the USA have at least over 100 chemical toxicants. Other sources claim much more.
Futhermore, newly built orremodeled buildingscan have substantial amounts of chemical “off-gassing” (9) Carpetscan release several neurotoxins. In one published study, the testing of over 400 carpet samples showed neurotoxins to be present in more than 90 percent of the samples, quantitatively sufficient in some samples to cause death in mice. (10) Even within the EPA headquarters where seventy-one ill employees evacuated the new EPA complex as a result of new carpet being installed. (11)
Carpets also trap toxicants like glyphosate that residents pick up on their feet and other environmental toxins from the air and ground. In this perspective, the “Non-Occupational Pesticide Exposure Study” (NOPES) found an average of 12 pesticide residues per carpet sampled,and determined that this route of exposure likely provides infants with nearly all of their non-dietary exposure to the notorious pesticides DDT, aldrin, atrazine, and carbaryl. (12). Bottom line, from the health viewpoint, it may be better to be poor and live in a mud house or cave and play in the dirt as our ancestors did for millions of years.
Xenobiotic Metabolism in Evolutionary Perspective
The driving force in the evolution of sophisticated metabolic detoxification systems appears to be dependent on the ability of water to act as a solvent to dissolve toxic substances. Since cellular membranes are primarilylipid based and impermeable to most water soluble(scientifically: “polar”) substances, the transport of water-soluble compounds into a cell requires specialized transport proteins.By placing the appropriate transport proteins on the cell membrane, a cell will only allow desirable water-soluble molecules to enter, and willprevent entry of water-soluble toxins.This same mechanism also applies when the cell needs to excrete unwanted water soluble compounds (like cellular wastes); they exit the cell by a similar mechanism.
In contrast to water-soluble compounds, thelipid cell membrane presents little barrier to lipid-soluble compounds, which can freely pass through it. Potentially damaging lipid-soluble toxins can therefore gain free access to the cell’s inner home. And these are much more difficult to remove.
Evolutionary biology fine-tuned the metabolic detoxification system byconverting lipid-soluble toxins into inactive water-soluble metabolites.The “solubilization” of a toxin is accomplished by enzymes which attach (conjugate) additional water-soluble molecules to the lipid-soluble toxin at specific attachment points. If the toxin does not contain any of these attachment points, they are first added by a separate set of enzymes which chemically transform the toxin to include these molecular “handles”. Following the solubilization reactions, the chemically-modified toxin is transported out of the cell and excreted.
These three steps or phases of removing undesirable or harmful lipid-soluble compounds are performed by three sets of cellular proteins or enzymes, called the phase I (transformation) and phase II (conjugation) enzymes, and the phase III (transport) proteins.
Phase I, II, and III metabolisms have different biochemical requirements andrespond to different metabolic signals, but must work in unison for proper removal ofunwanted xenobiotics (such as toxins or drugs) or endobiotics (such as excess hormones). Enzymes of the phase I, II, and III pathways have several characteristics that make them well suited for their important roles. (13) 19
Unlike most other enzymes, detoxification enzymes; can react with many different compounds, thereby broadening the number of toxins a single enzyme can metabolize. They are also more concentrated in areasof the body that are most directly exposed to the environment (like the liver, intestines, or lungs). Accompanied with a feedback system, they are inducible, meaning that their synthesis can be increased in response to toxin exposure.
The liver is the primary detoxification organ; itfilters blood coming directly from the intestines and prepares toxins for excretion from the body. Significant amounts of detoxification also occur in the intestine, kidney, lungs, and brain, with phase I, II, and III reactions occurring throughout the rest of the body to a lesser degree.
The Three Phases of Detoxification
Phase I Detoxification : Enzymatic Transformation
Under most circumstances, Phase I enzymes begin the detoxification process by chemically transforming lipid soluble compounds into water soluble compoundsin preparation for phase II detoxification. The bulk of the phase I transformation reactions are performed by afamily of enzymes called the cytochrome P450s (CYPs).
CYP enzymes are relatively non-specific and quite flexible, each has the potential to recognize and modify countless different toxins. A mere 57 human CYPs must be able to detoxify any potential toxin that enters the body. (14) With today’s 80,000 chemical toxicants released from today’s Industry, these 57 enzymes have to take time and energy off from their task of processing endotoxins, the body’s metabolic waste, to solubilize and excrete this onslaught of man-made toxicants.
While the CYPs are able to mobilize en mass against the foreign “enemy”, the cost of this versatility is speed, as these CYPs metabolize toxins very slowly compared to other enzymes. For instance compare the predominant CYP3A4, which metabolizes 1-20 molecules per second, (15) tosuperoxide dismutase (SOD), which metabolizes over a million molecules per second. Major sites of detoxification overcome the slower speed by producing large amounts of CYPs – CYPs may represent up to 5% of total liver proteins, and similar large concentrations can be found in the intestines. CYPs are amongst the most well studied and best characterized detoxification proteins due to their role in the metabolism of prescription drugs, and to their role in metabolizing endogenous biochemicals (for example,the enzyme aromatase, which transforms testosterone to estradiol, is a CYP.) (16)”
Several other enzymes contribute to the phase Iprocess as well, notably: the flavin monooxygenases (FMOs; responsible for the detoxification of nicotine from cigarette smoke); alcohol and aldehyde dehydrogenases (which metabolize drinking alcohol), and monoamine oxidases (MAO’s; which break down serotonin, dopamine, and epinephrine in neurons and are targets of several older antidepressant drugs) (17)
Phase II Detoxification – Enzymatic Conjugation
Following phase I transformation, the original lipid-soluble toxin has been converted into a more water-soluble form, however, this reactive intermediate is still unsuitable for immediate elimination from the cell for a couple of reasons: 1) phase I reactions are not sufficient to make the toxin water-soluble enough to complete the entire excretion pathway; and 2) in many cases, products from the phase I reactions have been rendered more reactive then the original toxins, which makes them potentially more destructive than they once were. Both of these shortcomings are addressed by the activities of the phase II enzymes, which modify phase I products to both increase their solubility and reduce their toxicity. For example, the activation of the phase II enzymes is responsible for the anti-mutagenic and anti-carcinogenic properties of the metabolic detoxification systems. It is now widely accepted that phase II enzymes protect against chemical carcinogenesis, especially during the initiation phase of cancers. (18)
At thegenetic level, the production of most phase II enzymes is controlled by a protein called nuclear factor erythroid-derived 2 (Nrf2), a master regulator of antioxidant response. (19) Under normal cellular conditions, Nrf2 resides in the cytoplasm (the liquid inside cells within which the cells components are contained) of the cell in an inactive state. (20) However, the presence of oxidative stress (triggered by metabolism of toxins by CYPs) activates Nrf2,allowing it to travel to the cell nucleus. (21) In the cell nucleus, Nrf2 turns on the genes of many antioxidant proteins, including the phase II enzymes. (22) In this way, Nrf2 “senses” oxidative stress or the presence of toxins in the cell, and allows the cell to mount an appropriate response.Nrf2 regulates the activity of genes involved in the synthesis and activation of important detoxification molecules including glutathione and superoxide dismutase (SOD). It also plays an important role in initiating heavy metal detoxification, and the recycling of CoQ10, a potent antioxidant. (23, 24, 25)
Certain dietary constituents (including sulforaphanefrom broccoliand xanthohumolfrom hops) may also directly activate Nrf2 and stimulate antioxidant enzyme activity; this may partially explain their beneficial effects on detoxification. (26)
There are several families of phase II enzymes that differ significantly in their activities and biochemistry. In several cases, phase II enzymes exhibit redundancy; a particular xenobiotic or endobiotic can be detoxified by more than one phase II enzyme.
UDP-glucuronlytransferases (UGTs)catalyze glucuronidation reactions, the attachment of glucuronic acid to toxins to render them less reactive and more water-soluble. There are several different UGTs that are distributed throughout the body, with the liver being the major location. In humans, many xenobiotics, environmental toxicants, and 40-70% of clinical drugs are metabolized by UGTs. (27)
In this perspective, the plasticizer bisphenol A (28) and benzopyrene (from cooked meats) (29) are two notable examples of UGT substrates (a substrate is a molecule upon which an enzyme acts). Intestinal UGTs may affect oral bioavailability of several drugs and dietary supplements, and may be responsible for chemoprevention in tissue. (30).
As for Glutathione S-transferases (GSTs), this enzyme catalyzes the transfer of glutathione (a significant cellular antioxidant) to phase I products. GSTs play a major role in the metabolism of several endobiotics, including steroids, thyroid hormone, fat-soluble vitamins, bile acids, bilirubin and prostaglandins. (31) GSTs can also function as antioxidant enzymes, detoxifying free radicals (32) and oxidized lipids or DNA. (33). GSTs are soluble enzymes that are ubiquitous in nature and in humans, forming about 4% of the soluble protein in the human liver and present in several other tissues (including brain, heart, lung, intestines, kidney, pancreas, lens, skeletal muscle, prostate, spleen and testes). (34, 35) Products of GST conjugation can be excreted via bile, or can travel to the kidneys where they are further processed and eliminated in urine.
Sulfotransferases (SULTs)attach sulfates from a sulfur donor to endo or xenobiotic acceptor molecules. This reaction is important both in detoxification reactions, as well as normal biosynthesis (the addition of sulfate to chondroitin and heparin, for example, is catalyzed by specific SULTs. (36) SULTs play a major role in drug and xenobiotic detoxification, and the metabolism of several endogenous molecules (including steroids, thyroid and adrenal hormones, serotonin, retinol, ascorbate and vitamin D). (37) SULTs in the placenta, uterus, and prostate are thought to play a role in the regulation of androgen levels. (38) In contrast to other phase II enzymes, SULTs can convert a number of procarcinogens (such as heterocyclic amines from cooked meats) into highly reactive intermediates which may act as chemical carcinogens and mutagens. (39)
While the UGTs, GSTs, and SULTs catalyze the bulk of human detoxification reactions, several other phase II enzymes contribute to the process to a lesser, but still important extent, including:
Methyltransferase enzymescatalyze methylationreactions using S-adenosyl-L-methionine (SAMe) as a substrate. COMT (catechol O-methyltransferase) is a major pathway for eliminating excess catecholamine neurotransmitters (such as adrenaline or dopamine). Methylation reactions are one of the few phase II reactions that decrease water solubility (40)
Arylamine N-acetyltransferases(NATs): NATs detoxify carcinogenic aromatic amines and heterocyclic amines (41)
Amino acid conjugating enzymes: Acyl-CoA synthetase and acyl-CoA amino acid N-acyltransferases attach amino acids (most commonly glycine or glutamine) to xenobiotics. The food preservative benzoic acid is one example of a toxin metabolized by amino acid conjugation. (42)
Phase III Detoxification – Transport
Phase III transporters are present in many tissues, including the liver, intestines, kidneys, and brain, where they can provide a barrier against xenobiotic entry and a pump system to pump out endobiotics. (43) Since water-soluble compounds require specific transporters to move in and out of cells, phase III transporters are necessary to excrete the newly formed phase II products out of the cell. Phase III transporters belong to a family of proteins called the ABC transporters (for ATP-Binding Cassette (44)), because theyrequire chemical energy, in the form of ATP, to actively pump toxins through the cell membrane and out of the cell. (45) They are sometimes called the Multidrug Resistance Proteins (MRPs), because drug-resistant cancer cells use them as protection against chemotherapy drugs.(46)
In the liver,phase III transporters move glutathione, sulfate, and glucuronide conjugatesout of cells into the bile for elimination. In the kidney and intestine, phase III transporters can remove xenobiotics from the blood for excretion from the body. (47)
Balance of Phase I and Phase II Reactions
The products of phase I metabolism are potentiallymore toxic than the original molecules, which does not present a problem if the phase II enzymes are functioning at a rate to rapidly neutralize the phase I products as they are formed. This, however, is not always the case. Factors which increase the ratio of phase I to phase II activity can upset this delicate balance, producing harmful metabolites faster than they can be detoxified, and increasing the risk of cellular damage.
Some of the factors include: diet (somefoods and supplements increase phase I enzyme activity), smoking and alcohol consumption (both induce phase I, so wine in moderation can be good), age (which can decrease phase II UGT, GST, and SULT activity), sex (premenopausal women show 30-40% more phase I CYP3A4 activity than men or postmenopausal women), disease, and genetics.
An illustrative example of the consequences of phase I/phase II imbalance is toxicity caused by overdose of the analgesic acetaminophen (paracetamol) – the active ingredient in Tylenol®. Acetaminophen toxicity is the most common cause of liver failure in the US. (48) With a normal therapeutic dose of acetaminophen, the drug is predominantly detoxified by the phase II UGT and SULT enzymes. A small amount of the drug is detoxified by a third mechanism: it is first transformed into the toxic metabolite NAPQI (N-acetyl-p-benzoquinoneimine) by phase I CYP enzymes; and this intermediate is detoxified by conjugation with glutathione using the phase II enzyme GST.
Duringacetaminophen overdose, the UGT and SULT enzymes become quickly overwhelmed.Proportionally more of the drug undergoes the third detoxification mechanism (transformation to NAPQI and conjugation by GST). Eventually, activity of the phase II GST enzyme slows as glutathione stores become depleted(49), and NAPQI is produced faster than it can be detoxified. Rising levels of NAPQI in the liver cause widespread damage, including lipid peroxidation, inactivation of cellular proteins, and disruption of DNA metabolism. (50) Treatment for acetaminophen overdose involves the timely replenishment of glutathione stores through administration of the precursor amino acids for glutathione synthesis (most commonly N-acetyl cysteine (51)
Complementary Mechanisms of the Detoxification Process
Following are several other mechanisms work in concert with the phase I, II, and III enzyme systems to improve their efficiency as well as to extend their functionality. While not officially characterized as part of xenobiotic metabolism, they are nonetheless important for reducing or mitigating toxin exposure.
Bile secretionis a critical digestive process for the absorption of dietary fats and fat-soluble nutrients. Bile also functions as themajor mechanism for moving conjugated toxins out of the liver and into the intestines, where they can be eliminated.
Antioxidationis a necessary protective measure against the harsh phase I oxidation reactions, which frequently produce free-radical byproducts. The production of antioxidant enzymes, many of which are under the same genetic regulation (by Nrf2) as the phase II enzymes, is important for minimizing this free-radical damage.
Heavy metal toxicitycan lead to oxidative damage by direct generation offree radical species and depletion of antioxidant reserves.(52)Mercury, arsenic, and lead, for example, effectively inactivate the glutathione moleculeso it is unavailable as an antioxidant or as a substrate for xenobiotic detoxification (53). This can also reduce the activity of the enzymes that recycle glutathione (54) One method for heavy metal removal is their chelation by the cellular proteins metallothioneins (MTs), which have a high capacity to bind various reactive metal ions, such as zinc, cadmium, mercury, copper, lead, nickel, cobalt, iron, gold, and silver. (55) One molecule of MT can bind 7–9 zinc or cadmium ions (or any combination of these two), up to 12 copper ions, and up to 18 mercury ions. (56) Cellular stress (particularly oxidative stress), turns up MT production, which, like the phase II enzymes, is stimulated by the activity of Nrf2. (57)
Prevention of absorptionthrough trapping of potential toxins (such as surface adhesion to another molecule in the gut, like activated charcoal or kaolin clay(58)) is an effective means of mitigating exposure; this mechanism has the requirement of some dietary adsorbent to be taken while the toxin is in transit in the GI tract. Uptake of potential toxins and their detoxification by beneficial colonic microfloracould have a similar effect.
To summarize the key points, metabolic detoxification is centered on the biochemical process of removing unwanted lipid-soluble compounds from the body. These “unwanted” compounds can be foreign (such as an environmental toxicants) or endogenous (toxins; such as excess hormone) in nature. Detoxification reactions occur throughout the body, with the liver being the predominant detoxifying organ. Detoxification reactions follow three steps or “phases” that have the ultimate goal of converting the toxin into an inert, water-soluble form for excretion: Phase Ireactions transform the toxin into a chemical form that can be metabolized by the phase II enzymes. Phase I reactions are performed primarily by the cytochrome P450 enzymes. Phase IIreactions conjugate (attach) the toxin to other water-soluble substances to increase its solubility. Each of the different types of phase II enzymes catalyzes a different type of conjugation reaction. UDP-glucuronlytransferases (UGTs) catalyze the glucuronidation of most clinical drugs, and several environmental toxins. Glutathione-S-transferases (GSTs) conjugate toxins with the antioxidant glutathione; they can also directly detoxify free radicals. Sulfotransferases (SULTs) catalyze sulfonation reactions; they may also be important for controlling sex hormone levels. Other types of phase II reactions that are used less frequently include methylationand amino acid conjugation reactions. Phase IIIdetoxification involves the transport of the transformed, conjugated toxin into or out of cells. Different phase IIItransport proteins work in concert to shuttle toxins from different parts of the body into bile or urine for excretion.
Following detoxification reactions, the toxins are removed from the body by excretion: First off, products of liver detoxification often leave the body by being secreted into the intestines in bile, but can sometimes be transported into the bloodstream for processing by the kidneys. Thereafter, the cells that line the intestines can detoxify toxins as they are absorbed, andrelease them back into the intestinal lumen. Lastly, the kidneys can filter and further process toxins from circulation, excreting them from the body as urine.
Metabolic detoxification is one of the most important restorative and longevity optimization functions that all sentient beings can modulate favorably. As Jean Bernard stated often, it’s all a question of the milieu’s back and forth struggle, the body’s anabolic and catabolic ups and downs, to compensate and restore homeostasis, the dynamic equilibrium of Life, at least for a few more milllions of years until Humans will be able to shift into the unified twilight zone.
Ch. Joubert (Director of H.M. Institute)
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This pathway (which will be referred to as metabolic detoxification) involves a series of enzymatic reactions that neutralize and solubilize toxins, and transport them to secretory organs (like the liver or kidneys), so that they can be excreted from the body.
Metabolic Detoxification. Each year, more than 4 billion pounds of potentially harmful chemicals are released into the environment, which can accumulate in the body and impact overall health.
Dec 22, 2009 – Metabolic detoxificationis a complex process involving a chain of chemical reactions that occur primarily within the liver and kidneys: Phase I (functionalization): Enzymes secreted by the liver break down toxins into modified, highly reactive molecules.
Nov 30, 2009 – In Part One of this series I discussed the Four R Program. Today I will focus on a therapy called “Metabolic Detoxification.” Years ago, the term “detoxification” was often only applied to a program for those with a drug or alcohol abuse issue, but today there are much broader and more significant applications …
Oct 12, 2015 – The article “Modulation of Metabolic DetoxificationPathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application” is misleading in its title and the discussion does not fit this title. This narrative review article presents a comprehensive review of food and food …
Jun 16, 2015 – Thus, the purpose of this review article is to summarize the science to date on the influence of whole foods, with a special focus directed towards phytonutrients and other food-based components, on influencing specific metabolic detoxificationpathways, including phase I cytochrome enzymes, phase II …
Metabolic Detoxification. Additional Aspects of the Detoxification Process. Several other mechanisms work in concert with the phase I, II, and III enzyme systems to improve their efficiency or extend their functionality. While not officially characterized as part of xenobiotic metabolism, they are nonetheless important for …
Looking for online definition of metabolic detoxificationin the Medical Dictionary? metabolic detoxificationexplanation free. What is metabolic detoxification? Meaning of metabolic detoxificationmedical term. What does metabolic detoxificationmean?
The Phases of Metabolic DetoxificationThe body’s natural cleansing or filtering process primarily involves the liver, digestive tract, lungs, and kidneys. Unwanted or potentially hazardous compounds that are soluble in water are easily eliminated (e.g., stool, sweat, urine). But fat-soluble compounds require enzymes from the …
https://www.livestrong.com › Weight Management
Jul 18, 2017 – Trendy detoxdiets are meant to help your body rid itself of harmful substances. Your metabolismis your calorie-burning system. While certain diets may affect your body’s metabolicrate, you cannot “detox” your metabolism; however, low- calorie detoxdiets may slow it down. If you’re considering a detoxdiet …
Reference and Precision Notes
1. Prakash AS, Pereira TN, Reilly PE, Seawright AA. Pyrrolizidine alkaloids in human diet. Mutat Res 1999;443(1-2):53-67
2. Borchers A, Teuber SS, Keen CL, Gershwin M. Food safety. Clin Rev Allergy Immunol 2010;39 (2) : 95-141
3. Ferguson LR, Philpott M. Nutrition and mutagenesis. Annu Rev Nutr 2008;28:313-29
4. Crinnion MJ. Environmental Medicine, Part 2 – Health Effects of and Protection from Ubiquitous Airborne Solvent Exposure. Altern Med Rev 2000;5 (2) : 133-143
5. Nielsen GD, Larsen ST, Olsen O, et al. Do indoor chemicals promote development of airway allergy? Indoor Air 2007;17 (3) : 236-55
6. Wallace LA, Pellizzari ED, Hartwell TD, et al. Personal exposure, indoor-outdoor relation- ships, and breath levels of toxic air pollutants measured for 355 persons in New Jersey. EPA 0589.
7. Hill RH Jr, Ashley DL, Head SL, et al. p- Dichlorobenzene exposure among 1,000 adults in the United States. Arch Environ Health 1995;50:277-280.
8. Broad scan analysis of the FY82 national human adipose tissue survey specimens. EPA Office of Toxic Substances. EPA 560/5-86- 035.
9. Ruhl RA, Chang CC, Halpern GM, Gershwin ME. The sick building syndrome. II. Assess- ment and regulation of indoor air quality. J Asthma 1993;30:297-308.
10. Duehring C. Carpet, EPA stalls and industry hedges while consumers remain at risk. Informed Consent 1993;1:6-32
11. Crinnion MJ. Environmental Medicine, Part 2 – Health Effects of and Protection from Ubiquitous Airborne Solvent Exposure. Altern Med Rev 2000;5 (2) : 133-143
12. Whitemore RW, Immerman FW, Camann DE, et al. Non-occupational exposures to pesticides for residents of two U.S. cities. Arch Environ Contam Toxicol 1994;26:47-59.
(13). Jakoby WB and Ziegler DM. The enzymes of detoxication. J Biol Chem 1990;265(34):20715-8
(14). Redlich G, Zanger UM, Riedmaier S, et al. Distinction between human cytochrome P450 (CYP) isoforms and identification of new phosphorylation sites by mass spectrometry. J Proteome Res 2008; 7 (11):4678-88
(15). Dai D, Tang J, Rose R, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 2001;299 (3):825-31
(16). Lardone MC, Castillo P, et al. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. Int J Androl. 2010 Aug 1;33(4):650-60. Epub 2009 Nov 3.
(17) Johnson R. Physiology of the gastrointestinal tract, Volume 1 – Page 1827. (2006) : 2000
(18). Nakamura Y, Miyamoto M, Murakami A et al. A phase II detoxification enzyme inducer from lemongrass: identification of citral and involvement of electrophilic reaction in the enzyme induction* 1. Biochemical and … (2003)
(19). Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA 1994;91 (21) : 9926-30
(20). Kobayashi A, Kang MI, Okawa H, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol 2004;24 (16) : 7130-9
(21). Motohashi H and Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 2004;10 (11) : 549-57
(22). Jung KA and Kwak MK. The Nrf2 system as a potential target for the development of indirect antioxidants. Molecules 2010;15 (10) : 7266-91
(23) Landi L, Fiorentini D, Galli MC, Segura-Aguilar J, Beyer RE. DT-Diaphorase maintains the reduced state of ubiquinones in lipid vesicles thereby promoting their antioxidant function. Free Radic Biol Med 1997;22 (1-2) : 329-35
(24). Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997;236 (2) : 313-22
(25). Klaassen CD and Slitt AL. Regulation of hepatic transporters by xenobiotic receptors. Curr Drug Metab 2005;6 (4) : 309-28
(26). Dinkova-Kostova AT, Holtzclaw WD, Cole RN et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA 2002;99 (18) : 11908-13
(27). Jancova P, Anzenbacher P, Anzenbacherova E. Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154 (2) : 103-16
(28). Mazur CS, Kenneke JF, Hess-Wilson JK, Lipscomb JC. Differences between human and rat intestinal and hepatic bisphenol A glucuronidation and the influence of alamethicin on in vitro kinetic measurements. Drug Metab Dispos 2010; 38 (12): 2232-8
(29). Tukey and Strassburg. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 2000; 40 pp. 581-616
(30). Van der Logt EM, Roelofs HM, van Lieshout EM, Nagengast FM, Peters WH. Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases. Anticancer Res 2004;24 (2B) : 843-9
(31). van Bladeren PJ. Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 2000;129 (1-2) : 61-76
(32). Sheehan D, Meade G, Foley VM, Dowd CA. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 2001;360 (Pt 1) : 1-16
33. Ketterer B. Glutathione S-transferases and prevention of cellular free radical damage. Free Radic Res 1998;28 (6) : 647-58
34. van Bladeren PJ. Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 2000;129 (1-2) : 61-76
35. Hayes JD and Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000;61 (3) : 154-66
36. Habuchi O. Diversity and functions of glycosaminoglycan sulfotransferases. Biochim Biophys Acta 2000;1474 (2) : 115-27
37. Glatt H and Meinl W. Pharmacogenetics of soluble sulfotransferases (SULTs). Naunyn Schmiedebergs Arch Pharmacol 2004;369 (1) : 55-68
38. Coleman. Human Drug Metabolism: An Introduction. (2010) pp. 360
39. Jancova P, Anzenbacher P, Anzenbacherova E. Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154 (2) : 103-16
40. Jancova P, Anzenbacher P, Anzenbacherova E. Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010;154 (2) : 103-16
41. Mulder GJ. Conjugation reactions in drug metabolism: an integrated approach : substrates, co-substrates, enzymes and their interactions in vivo and in vitro. Taylor and Francis, 1990. 413 pages
42. Hodgson. A Textbook of Modern Toxicology. (2010) pp. 672
43. 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 (9) : 6332-48
44. Keppler D. Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol 2011;201 : 299-323
45 Mizuno, N.; Niwa, T.; Yotsumoto, Y.; Sugiyama, Y. Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 2003, 55, 425-461.
46. Klaassen C and Lu H. Xenobiotic Transporters: Ascribing Function from Gene Knockout and Mutation Studies. Toxicological Sciences 2008;101 (2) : 186-196
47. Klaassen C and Lu H. Xenobiotic Transporters: Ascribing Function from Gene Knockout and Mutation Studies. Toxicological Sciences 2008;101 (2) : 186-196
48. Liska DJ. The Detoxification Enzyme Systems. Altern Med Rev 1998;3 (3) : 187-198
49. Larson et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005;42 (6) : 1364-72
50. Moyer AM, Fridley BL, Jenkins GD et al. Acetaminophen-NAPQI Hepatotoxicity: A Cell Line Model System Genome-Wide Association Study. Toxicol Sci 2011;120 (1) : 33-41
51. Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Rev Toxicol 2001; 31 (1): 55-138
52. Lauterburg BH, Corcoran GB, Mitchell JR. Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest 1983; 71 (4): 980-91
53. Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001;1 (6) : 529-39
54. Costa M. In vitro assessment of the toxicity of metal compounds. Biological Trace Element Research 1984;
55. Patrick L. Lead. Altern Med Rev 2006;11 (2) : 114-127
56 Nordberg M. Metallothioneins: historical development and overview. Met Ions Life Sci 2009;
57. Sabolić I, Breljak D, Skarica M, Herak-Kramberger CM. Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals 2010);23 (5) : 897-926
58. Nordberg M. Metallothioneins: historical review and state of knowledge. Talanta 1998; See also. Phillips TD, Lemke SL, Grant PG. Characterization of clay-based enterosorbents for the prevention of aflatoxicosis. Adv Exp Med Biol 2002;504 : 157-71 . Guengerich FP. Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. Am J Clin Nutr 1995;61 (3 Suppl) : 651S-658S. Guengerich FP. Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. Am J Clin Nutr 1995;61 (3 Suppl) : 651S-658S
Disclaimer: Nothing in this educational blog should be construed as medical advise. Only the State controlled certified synthetic drug and surgery pushing conventional doctors have the monopoly of “real” medicine, the result of which is to have become one of the first causes of collective suffering and premature death ever.
2018 (c). Happiness Medicine Institute et al.
Detoxificationor detoxication(detoxfor short)is the physiologicalor medicinalremoval of toxicsubstances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of withdrawalduring which an organism returns to homeostasisafter long-term use of an addictivesubstance.In medicine, detoxification can be achieved by decontamination of poison ingestionand the use of antidotesas well as techniques such as dialysisand (in a limited number of cases) chelation therapy.
Many alternative medicinepractitioners promote various types of detoxification such as detoxification diets. Scientists have described these as a “waste of time and money”.Sense About Science, a UK-based charitable trust, determined that most such dietary “detox” claims lack any supporting evidence.
Alcohol detoxification is a process by which a heavy drinker’s system is brought back to normal after being habituatedto having alcohol in the body continuously for an extended period of substance abuse. Serious alcohol addiction results in a downregulation of GABAneurotransmitterreceptors. Precipitous withdrawalfrom long-term alcohol addiction without medical management can cause severe health problems and can be fatal. Alcohol detox is not a treatment for alcoholism. After detoxification, other treatments must be undergone to deal with the underlying addiction that caused the alcohol use.
Clinicians use drug detoxification to reduce or relieve withdrawalsymptoms while helping an addicted individual adjust to living without drug use; drug detoxification does not aim to treat addiction but rather represents an early step within long-term treatment. Detoxification may be achieved drug-free or may use medications as an aspect of treatment. Often drug detoxification and treatment will occur in a community program that lasts several months and takes place in a residential setting rather than in a medical center.
Drug detoxification varies depending on the location of treatment, but most detox centers provide treatment to avoid the symptoms of physical withdrawal from alcohol and from other drugs. Most also incorporate counselingand therapy during detox to help with the consequences of withdrawal.
An animal’s metabolismcan produce harmful substances which it can then make less toxic through reduction, oxidation(collectively known as redoxreactions), conjugationand excretionof molecules from cells or tissues.This is called xenobiotic metabolism.Enzymes that are important in detoxification metabolism include cytochrome P450 oxidases,UDP-glucuronosyltransferases,and glutathione S-transferases.These processes are particularly well-studied as part of drug metabolism, as they influence the pharmacokineticsof a drug in the body.
Certain approaches in alternative medicineclaim to remove “toxins” from the body through herbal, electrical or electromagnetic treatments. These toxinsare undefined and have no scientific basis,making the validity of such techniques questionable. There is little evidence for toxic accumulationin these cases,as the liverand kidneysautomatically detoxify and excrete many toxic materials including metabolicwastes. Under this theory if toxins are too rapidly released without being safely eliminated (such as when metabolizing fat that stores toxins) they can damage the body and cause malaise. Therapies include contrast showers, detoxification foot pads, oil pulling, Gerson therapy, snake-stones, body cleansing, Scientology‘s Purification Rundown, water fasting, and metabolic therapy.
- Chelation therapy(heavy metal detoxification)
- New York Rescue Workers Detoxification Project
- Organisms used in water purification
- “detoxification – definition of detoxification by the Free Online Dictionary, Thesaurus and Encyclopedia”. Thefreedictionary.com. Retrieved 2013-04-21.
- “detoxify – definition of detoxify in the Medical dictionary – by the Free Online Medical Dictionary, Thesaurus and Encyclopedia”. Medical-dictionary.thefreedictionary.com. Retrieved 2013-04-21.
- “Toxicology Primer”. UIC. Archived from the originalon 2013-10-31. Retrieved 2013-04-21.
- “Get the Lead Out – Autumn 2009 Living Bird”. Birds.cornell.edu. Retrieved 2013-04-21.
- “Scientists dismiss detox schemes”. BBC News. 3 January 2006. Retrieved 5 May2013.
- “Detox diets: Do they work? – Mayo Clinic”. Retrieved 26 July2016.
- “Scientists dismiss detox schemes”. 3 January 2006. Retrieved 26 July2016– via bbc.co.uk.
- No proof so-called detox products work: scientists[permanent dead link]
- “Archived copy”. Archived from the originalon 2009-08-04. Retrieved 2009-07-18.
- xenobiotic metabolic process (2013-04-13). “AmiGO: xenobiotic metabolic process Details”. Amigo.geneontology.org. Archived from the originalon 2009-07-25. Retrieved 2013-04-21.
- L-60: Xenobiotic Metabolism(archived version).
- “Metabolism of Xenobiotics”. Zoology.muohio.edu. Archived from the originalon 2013-06-01. Retrieved 2013-04-21.
- Xenobiotic Metabolism-Oxford Biomedical Research Inc(archived version).
- Danielson P (2002). “The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans”. Curr Drug Metab. 3(6): 561–97. doi:10.2174/1389200023337054. PMID 12369887.
- King C, Rios G, Green M, Tephly T (2000). “UDP-glucuronosyltransferases”. Curr Drug Metab. 1(2): 143–61. doi:10.2174/1389200003339171. PMID 11465080.
- Sheehan D, Meade G, Foley V, Dowd C (2001). “Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily”. Biochem J. 360(Pt 1): 1–16. doi:10.1042/0264-6021:3600001. PMC 1222196. PMID 11695986.
- “Small Molecule Drug Metabolism”. Ionsource.com. 2012-09-01. Retrieved 2013-04-21.
- “Comparison of the Levels of Enzymes Involved in Drug Metabolism between Transgenic or Gene-knockout and the Parental Mice”. Tpx.sagepub.com. 2001-01-01. Retrieved 2013-04-21.
- D M Dulik & C Fenselau (1988-04-01). “Use of immobilized enzymes in drug metabolism studies”. Fasebj.org. Retrieved 2013-04-21.
- “More information on complementary and alternative medicine – American Cancer Society”. Retrieved 26 July2016.