Detox & Biotransformation - What Is It?

The Process

1. Biotransformation/detoxification is a metabolic process the body uses to remove unwanted hydrophobic substances (water hating) from either exogenous (foreign) or endogenous (made in the body) sources through transforming them into more hydrophilic (water loving) substances that are easier to remove.
2. Biotransformation/detoxification occurs throughout the whole body. However, the main areas for serious biotransformation to take place are in the liver and intestines.
3. There are three steps involved: Phase I, Phase II, Phase III -
   • Phase 1 is about introducing a functional group or exposing a functional group and making the substance more water soluble.
   • Phase two is about conjugation of the functional groups, making the substance more water soluble.
   • Phase III is about using transport mechanisms to get the substance past the cell membrane and out of the cell.
4. The Liver, Intestines and Kidneys are key players in transformation/detoxification, although all cells in the body partake of this process to some degree or another.
   

Cell Membranes And Toxins

Cell membranes are primarily lipid or oil based. They are largely impermeable to polar (water-soluble) substances.  A water-soluble substance requires assistance to get across the cell membrane . This assistance is available from specialized transport proteins in the cell membrane. The cell only allows desirable water-soluble molecules into the cell and will not allow entry of water-soluble toxins. The cell excretes unwanted water-soluble substances with transport proteins also.

Since the cell membrane is made  out of lipids,  fat-soluble substances can move into and through the lipid membrane more easily and without assistance. This allows lipid-soluble toxins easier access to the inside of the cell where they can build up if not removed.

Ingested toxins that are fat soluble are more easily absorbed by the intestines. Fat-soluble (non-polar) substances often end up stored in fat tissue.

How The Body Deals With These Fat Soluble Toxins

The body has provided an enzymatic biotransformational/detoxification system to change these lipid-soluble toxins into less active/less toxic water-soluble substances. Generally this is done via the “Phase II enzymatic system” by the conjugation (joining) of water-soluble molecules to the lipid-soluble toxin at specific attachment points. When the toxic substance does not have attachment points, the body can use parts of the enzymatic system called “Phase I”  to transform the toxin so it has attachment points and now allow Phase II to attach water soluble molecules to it.

Once the substance is made water-soluble it can be excreted out of the cell by means of the transport/carrier proteins. Because it is changed to be more polar, and more water soluble, this means it is hard now for this substance to move through the lipid bi-layer of the cells protective membrane. However,  a transport/carrier protein can escort it across the membrane just as a mom would pick up and escort a three year old across a sidewalk. This transportation of the toxin out of the cell is called “Phase III” of the biotransformational/detoxification system. Phase III can involve transport of transformed substances both out of or into a cell. In addition, phase III transport/carrier proteins have the job of shuttling toxins into the bile or urine for excretion from the body.

 

The Three Phases of Biotransformation/Metabolic Detoxification in a nutshell

There is a three step enzymatic process for the transformation , neutralization and removal of unwanted chemical compounds. These are classified as Phase 1, Phase II and Phase III.

Phase I

Phase I reactions are generally reactions which modify a substance by adding a functional group to it or exposing a preexisting function group. This allows the substance to become conjugated with another substance in phase II. Sometimes phase I transforms the substance so it can be immediately excreted from the body. Often times compounds made in Phase 1 actually become more toxic and this is called a bioactivation reaction. Luckily, phase II takes over at that point.

Phase II

Phase II reactions are those reactions that conjugate (join together) the modified substance with another substance. The conjugated products are larger than the original substrate and generally polar (water soluble). Being water soluble allows them to be more easily excreted from the body. Phase II also acts directly on compounds to conjugate them without the need of Phase I. It can only do this if the substance already has a functional group on it that can be conjugated. Conjugated compounds also have poor ability to cross cell membranes due to their increased water soluble nature, therefore phase III is needed for the water soluble toxin to be able to be removed from the cell.

Phase III

Phase III is the process of using transport/carrier proteins to remove the polar (water soluble) substance through the cell membrane. You can imagine stage III as the stage where the compound takes a taxi as it is leaving the neighborhood.

 

Where Toxins Come From

The body attempts to eliminate anything that is toxic or is in excess. Besides the usual things we think of as toxins, it can include everything form hormones and vitamins to inflammatory molecules and prescription drugs. Therefore the bodies biotransformational or detoxification processes protects us from endogenous as well as exogenous toxins. It also provides a mechanism of homeostasis.

 

The Main Route For Toxins To Enter the Body

A main route for toxins to enter the body is through the intestines. Hopefully, an ingested toxin will be altered by gut bacteria or removed in the feces, but if a toxic substance gets past the intestines, and into the body, it quickly ends up in the liver where biotransformation of substances is a fine art. The liver and intestines are two organs where you will find biotransformation/detoxification going at full speed. However biotransformation of toxins is available through-out the body. Remember, there are other routes of entry into the body. Environmental toxins/chemicals/drugs can also enter from the lungs, the skin, the eyes, vaginally, and rectally.

 

Diet

For most individuals, their diet is the largest source of toxin exposure. This can be from bacterial or fungal organisms on food, or it can be from farming practices where sewage sludge, herbicides, or pesticides were used. Food related toxins can also be from food preservatives, food additives, heavy metals, and even chemicals from the processing, or packaging of the food.

 

Toxins In The Environment

Buildings And Off Gassing

The next source of toxins comes from the environment. The number one source of toxins in most peoples environment comes from the buildings they live in, work in, or go to school in. Additionally, there are the buildings the person frequents, such as governmental buildings, or stores. The buildings are often built with potentially hazardous materials that off-gas toxicants. Something as simple as installing a new carpet in a home, can make a person extremely ill, depending on the carpet chemicals and the biotransformational capability of the person.  Products in stores people visit, or the items you purchase, and take home can be a potential source of off-gassing depending on what chemicals that item was made out of.

Buildings And Water-Damage

Additionally, if a building has water-damage, and is not remediated within 24-48 hours the growth of fungus, and microbes within the mix of chemical laden building materials becomes a nightmare. You may have a release of mycotoxins, bacterial endotoxins, beta glucans, mannans, proteinases, hemolysins, c-type lectins, and volatile organic compounds to name a few known toxins associated with water-damaged buildings. It is thought that as many as 50% of buildings in the United States have some sort of water-damaged. Often people do not know they are in a water-damaged building that was not remediated properly. There is no visible mold or bacteria, but the toxins still linger. They can be quite sickened by the environment without ever realizing what is causing it.

Toxins In Air, Water And Soil

Then we have other environmental toxins which are probably the ones most people think of first. These are things that pollute our water, air, and soil. They are being emitted from our vehicles, manufacturing processes, chemicals sprayed on lawns, ill-thought out agricultural practices and more things than you want me to list here. We have really created a chemical soup of toxins on the planet and our bodies are working hard to protect us all the time.

 

What Can Be Done

Limit Exposure

There are things people can do to limit their exposure to toxins. I suggest you visit the Environmental Working Group website to learn more about toxins in our environment, and how you can protect yourself and your patients. Learn how you can make changes in your community toward safer options.

Learn How To Support Your Biotransformation Process

Additionally, learning how the body transforms these toxins can give you ideas of which biotransformational processes are not working up to snuff and how to support those processes.

Genetics May Be A Key To The Puzzle For Some People

Keep in mind that gene polymorphism plays a role in how people are able to transform toxins into less toxic substances and remove them from the body.

There Are Many Layers Involved

Issues can stem from genetic polymorphisms, an over-worked system from too many exogenous or endogenous toxins, or a lack of nutrients available to support the biotransformational system. An understanding of the biochemical mechanisms involved in the regulation of these systems and the nutritional support necessary to keep these enzyme systems going, gives the practitioner a wonderful tool to help their patients. Practitioners also support the organs most involved in detoxification.

 

Powerhouse Organs Of Detoxification And Elimination

Biotransformation/Detoxification goes on everywhere in the body, but the powerhouses of detoxification lies in the liver and in the intestinal wall. Supporting these two body organs alone can give much needed support to the biotransforamtional/detox system.

 

Substances That Induce Biotransformation

A substance that activates Phase I and Phase II is known as a bifunctional inducer. If it activates only Phase II it is known as a monofunctional inducer.

 

Biotransformation Process And Collateral Damage

Compounds transformed through the biotransformational process include normal substances created by the body such as hormones, other signaling molecules as well as drugs, pesticides, insecticides, food additives, alcohol, mycotoxins, microbial toxins and other toxins from the gut. Anything that is toxic, or would become toxic at high levels goes through this process. These biotransformational processes also metabolize signaling molecules into other signaling molecules, allowing for variation in the activities of these substances.

The Collateral Damge

Phase I enzymes directly neutralize many chemicals, but some are transformed into intermediate forms that are then processed by phase II processes. These intermediate forms are often more chemically active and therefore can be more toxic. If the phase II detoxification systems are not working adequately, these intermediates can build up and cause substantial damage, including the initiation of carcinogenic processes or genetic mutations. Additionally free radicals can be created by the process.

The safest detoxification is when a substance undergoes a slow Phase I, followed by a more rapid Phase II. This prevents accumulation of Phase I metabolites which can be more toxic than their precursors.

Phase I Reactions

Oxidation, reduction and/or hydrolysis reactions are the main type of reactions taking place in Phase I. Antioxidants can help protect us from the reactive oxygen intermediates created in this process.

Antioxidants found To Be Useful In This Aspect:

• Vitamin A,
• Vitamin C
• Vitamin E
• Copper
• Manganese
• Selenium
• Zinc
• Coenzyme Q10
• Thiols (sulfurs in garlic, onions and mustard family plants)
• Bioflavonoids
• Silymarin (Milk thistle)

Once toxins are transformed they are eliminated via the kidneys in the urine, or excreted in the feces via the bile.

 

Overview Of Intestinal And Liver Activity Regarding Toxins

For the intestinal transformation to be working adequately, the small intestines need to be healthy. If the intestines can't keep up with the toxins coming through the food, the toxins will end up in the liver via the portal blood, and the biotransformational system in the liver removes what it can. Bile secretion by the liver is a critical process, and the main mechanism for moving conjugated toxins out of the liver and into the intestines.The liver needs to be functioning up to par to create adequate bile (made from cholesterol) and the gall bladder needs to also be intact and working well to concentrate, and store the bile for excretion into the digestive tract, along with the toxins attached to the bile that are being eliminated with the bile into the intestinal tract. As long as the bile/toxin combo stays hooked up during intestinal transit, they will both be excreted out of the body as part of the feces.

The Intestines Are Constantly Detoxing

Drug/toxin-metabolizing enzymes within intestinal cells constitute a key barrier to toxin entry into the systemic circulation. Although the liver is considered the powerhouse of biotransformational processes, many toxins come into the body through the intestines. This makes the intestinal cells biotransformation/detoxification activities very important. The intestines perform Phase I, II and III enzymatic activity, but also contain intestinal gut microflora that produce substances which induce, or inhibit transformational activities. Additionally, there are pathogenic bacteria in the gut that release toxins which add to the biotransformational load on the body. Gut microflora also remove some conjugation moieties from substances that are in the enterohepatic circulation. This means toxins which were conjugated by the liver and are sent into the bile to be removed in the fecal mass, can be unconjugated and the toxin can re-enter the circulation in its original toxic form. (Gheeze Louise, can't an enterocyte (intestinal cell) get a break!)

The Intestines First Line Of Defence When A Toxin Gets Into A Cell

The intestines use  the antiporter system (also used elsewhere) called p-glycoprotein (or known as a multidrug resistant pump) which pumps foreign toxins (xenobiotics) out of the intestinal cells into the intestinal lumen. When the cell can not keep up with the xenobiotics coming in, this gives the cell another opportunity to metabolize the toxin the second time it shows up rather than allowing the toxin to move further into the cell where it can cause damage.

Influencing Factors on BIotransformational Capabilities

• Genetics
• Age
• Sex
• Lifestyle habits
• Nutrient availability
• Disease
• Presence of specific xenobiotics (including medications)
• The sheer number of toxins

Metallothionein Genetic Polymorphism

The genetic polymorphism of metallothioneins can also effect biotransformation/detoxification. Metallothioneins (MT) are proteins composed of about 30% cysteine. They are used for storage, transfer, and detoxification of intracellular metal ions. They are well known for their role in eliminating toxic metals. Metallothioneins bind toxic metals including cadmium, and mercury, and transport them to the liver, or kidneys where glutathione conjugation takes place, followed by excretion of the toxic metal in the urine or bile. In addition they transport and provide short-term storage for zinc and copper. Animals have shown a wide range of MT capability that is due to polymorphisms. There are also animal mutants that possess multiple copies of MT genes in their chromosomes, and have prolific upregulation of MT production. There is also some polymorphism seen in humans for MT expression.

Metallothioneins Can Be Increased

Gene expression for MT production is inducible through zinc supplementation, fasting and exercise.

Modulating The Detox System

A considerable amount of research has been undertaken to find substances that activate or supress the biotransformational pathways focusing on enzymes generally.

Obviously, it is beneficial to improve availability of enzymes to enhance the system, eliminate toxins as soon as possible. You might think that anything that increases activity of the Detox system would be beneficial, but the fact is that the toxins themselves increase the system activity. So, you want to provide the necessary nutrients, and non-toxic stimulants while avoiding those pathway stimulants that are toxic.

Additionally, it is important to note, that stimulation of phase I is contraindicated if the patient’s phase II systems are under active. If Phase II can't keep up with the reactive substances created by Phase I, those substances rendered more reactive by Phase I, will create additional damage before Phase II deals with them. This has to be kept in mind when approaching this subject.

The substances used to affect the biotransformational system are lumped into some broad classifications known as

• Substrates
• Inducers
• Inhibitors.

The substances that the biotransformation system works on are called substrates. The substances that increase any part of the biotransformational system are called inducers. The substances that decrease part of the biotransformational system are called inhibitors.
Exogenous substances requiring biotransformation may include toxins, drugs, nutrients, or herbal constituents. Toxins can be a variety of substances that are ingested, inhaled, or absorbed through the skin or some orifice of the body.

 

Substrates

A substrate is a material or substance that an enzyme acts upon. The substrate may be a toxin or hormone, or other exogenous or endogenous substance that is acted upon and undergoes biotransformation. A substrate is not necessarily a toxin but often can be. A substrate can also be a necessary substance for bodily functions.

Inducers

Something that activates enzymes, makes the enzyme work better, allows the enzyme to work or otherwise stimulates the process of biotransformation. Substrates usually induce the creation of enzymes needed to break them down. For this reason substrates are often included in the list of inducers.

Inhibitors

Something that deactivates enzymes, decreases the enzyme from working well or otherwise decreases biotransformation. Sometimes a substrate can cause competitive inhibition. In this case the substance is both a substrate and an inhibitor.

 

Inducer Examples

By and large, we are interested in inducers of biotransformational pathways. Therefore, this is what I am giving examples of in this general presentation of the detox system. Look to the individual articles on the biotransformational/detox pathways on this website for further details on individual pathway substrates, inducers and inhibitors.

 

Calcium D-glucarate

An example of an inducer that is decreasing an enzyme made by bacteria is calcium D-glucarate. Calcium D-glucarate is found in many fruits and vegetables. It induces glucuronidation by inhibiting an enzyme called beta-glucuronidase.  Beta-glucuronidase is an enzyme produced by gut bacteria and intestinal cells. Beta-glucuronidase removes (deconjugates) glucuronic acid from neutralized toxins (unconjugates them). This reverses the glucuronidation catalyzed by UGTs. Deconjugation reverts the toxin to its previous dangerous form, and allows it to be reabsorbed as part of the enterohepatic recycling. Elevated beta-glucuronidase activity has been associated with increased cancer risk. So calcium D-glucurate induces, or in this case protects glucuronidation through its activity in the gut on bacterial enzymes.

Flavonoids

Many flavonoid compounds can induce biotransformation activity of many of the Phase II enzymes. The flavonoid eriodictyol has been shown to increase expression of phase II enzymes that correlates wtih increased cell survival in oxidative stress settings. Long term treatment showing more benefit than short term treatment. (Johnson, 2009)

Cruciferous Vegetables

The Cruciferous vegetables are known for induction of Phase II. Cruciferous vegetables such as broccoli, bok choy and brussel sprouts, are especially known for their induction of glutathione s-transferase and glucuronyl transferases.

D-limonene

D-limonene found in citrus oil, has ben shown to induce both phase I and phase II. Research has shown it increases CYP450, intestinal UGT activity and liver GST and UGT activity in rats.

Chlorophyllin

Chlorophyllin derived from chlorophyll inhibits CYP450 activity as well as stimulates glutathione activity in rats. Chlorophyll and chlorophyllin also both trap toxins similar to charcoal thereby preventing absorption in the gut. They have also been shown to trap aflatoxins and keep them from being absorbed in animals. In human research it appears that co-consumption of these products with aflatoxin may limit the bioavailability of the ingested aflatoxin in humans, as takes place in animals.

Nrf2

Research indicates nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in increasing many phase-II drug-metabolizing genes as well as a number of efflux transporters in phase III that are important for the liver's removal of xenobiotics. It has minimal effect on Phase I CYP450 genes. It is also very involved in the production of antioxidant enzymes. This is an important point since phase I oxidation reactions produce a lot of free-radical byproducts, and sometimes it is better to stimulate phase II but not phase I.

Nrf2 increases many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S-transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly increases a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification. (Kai Connie Wu, 2012)

Nrf2 has been described as:

• Activator of cellular defense mechanisms
• Master redox switch and a guardian of health span
• Gatekeeper of species longevity

The major products of Nrf2 genes are

• Glutathione
• Glutathione-S-transferase
• Hemoxygenase-1
• Thioredoxin (non-enzyme)
• Thioredoxin reductase
• Quinone reductase
• NAD(P)H:Quinone oxido-reductase
• Ferritin
• Metallothionein
• Peroxisome proliferator-activated receptor
• Nuclear factor erythroid 2-related factor 2
• NADPH regenerative enzymes

(For descriptions of these names, see the terminology section at the bottom of the page.)

Activators of NrF2

Substances that activate Nrf2 will ultimate induce Phase II and gluathione production. Many herbs and foods have been found to activate NrF2. Some of them are  included in the liste below.

• Curcumin found in Turmeric - Curcuma longa
• Silymarin found in Milk thistle - Silybum marianum
• Resveratrol found in Japanese Knotweed - Polygonum cuspidatum
• Grape skin
• Red wine
• Dark colored berries
• Dark chocolate and raw cacao
• Green tea
• Broccoli sprouts
• Cinnamaldehyde found in Cinnamon - Cinnamomum spp., Alpha lipoic acid
• Alpha tocopherol
• Lycopene
• Apple polyphenols (chlorogenic acid and phloridzin)
• Gingko biloba
  Chalcone
• Capsaicin from Cayenne - Capsicum spp.
• Hydroxytyrosol from olives
• Allyl sulfides from Garlic - Allium sativum
• Chlorophyllin
• Xanthohumols from Hops - Humulus lupulus

Strongest Natural Activator Of Nrf2 Known

One of the strongest activators of NRF2 has been found to be the isothiocyanate called sulforaphane. Sulforaphane is the metabolite of glucoraphanin (GRN) which is contained in the cruciferous plants cell vacuole along with an enzyme called myrosinase (MYR) which are kept separate. When the plant cell wall ruptures and GRN and MYR come together, sulforaphane is enzymatically produced. All the Brassica/Crucifera plant family yields sulforaphane. The highest amounts are in broccoli and to be precise, broccoli sprouts. Cutting, chewing or otherwise opening the cell walls of these plants immediately causes synthesis of sulforaphane. However, it immediately begins to degrade. So, if you make yourself a broccoli drink you need to drink it sooner rather than later. You can find an artilce called "Detox With Broccoli"on this website.

Some Oddball Data I Found Entertaining

• The vitamin D receptor (VDR) is Nrf2 target gene inducible by sulforaphane. In turn, Vitamin D can increase Nrf2 expression.
• The redox-modulating activity of the frequently prescribed statins and ACE inhibitors has been attributed to their Nrf2 inducer ability. Gold salts, once the mainstay of treatment for rheumatoid arthritis, are Nrf2 inducers.
• There is an idea that because Nrf2 is activated by a mild prooxidant signal, high doses of antioxidant supplements may blunt signals required to activate endogenous defenses . (Muthusamy VR, Kannan S, 2012 & Magbanua M. J. M., 2014)

Activators of Quinone oxioreductase

Quinone oxioreductase is a phase II enzyme. There is a value called CD value(s CD value refers to the concentration of a compound required to double the activity of the Phase II detoxification enzyme, quinone reductase ) used for phytochemicals that activate quinone reductase. I have listed them here to give you a way to compare how some of these substances might differe in their ability to act as inducers for the phase II enzyme quinone oxioreductase. Note similarities with the activators of NRf2.

• sulforaphane (0.2 μM)
• Andrographolides (1.43), quercetin (2.50)
• β-carotene (7.2 μM)
• Lutein (μM)
• Resveratrol (21 μM
• Indole-3-carbinol from mature broccoli vegetable (50 μM),
• Chlorophyll (250 μM)
• α-cryptoxanthin (1.8 mM)
• Zeaxanthin (2.2 mM),
• Curcumin (2.7 μM)
• Silymarin (3.6 μM)
• Tamoxifen (5.9 μM)
• Genistein (16.2 μM)
• Epigallocatechin-3-gallate (EGCG) (>50 μM)
• Ascorbic acid (>50 μM)

The CD value of sulforaphane is 13.5-fold greater than that of curcumin, 18-fold greater than silymarin, and 105-fold greater than resveratrol.

The comparative inducer activity of NQO1 (quinone oxidoreductase 1 ) in these phytochemicals is sulforaphane > andrographolides > quercetin > curcumin > silymarin > tamoxifen > beta-carotene > genistein > lutein > resveratrol > I-3-C > chlorophyll > α-cryptoxanthin > zeaxanthin. (Christine A. Houghton, 2016)

Indole-3-carbinol

Besides sulpforaphane, another Brassicaseae plant derivative that stimulates Phase II and not Phase I is indole-3-carbinol. It is from the glucosinolate known as glucobrassicin and like sulforaphane is also a strong inducer of Nrf2. The enzyme myrosinase is needed for the hydrolysis of glucobrassicin into indole-3-carbinol(IC3). Myrosinase and glucobrassicin are contained in the brassica family plants but seperated from each other inside vaculoes. Once the plant cells are opened by chewing or cutting myrosinase is release along with glucobrassicin and hydrolysis changes glucobrassicin into indole-3-carbinol. Research shows myrosinase is also created by gut bacteria which would mean this would help make IC3 from glucorophanin. This means when cooking inactivates myrosinase, any glucorophanin still left from cooking may be altered to IC3 to some degree by gut bacteria.

Although, we may be interested in our biotransformation systems working up to par to keep us all healthy, we must remember we can have too much of a good thing at which point it is no longer beneficial. A case in point would be the newly tested drug Bardoxolone Methyl which was known to enhance glomerular filtration rate in patients with chronic kidney disease, a disease known to have significant oxidative stress. This drug was a synthetic analog of the triterpenoid called oleanolic acid, which is found in edible plants. and is known to have cytoprotective properties thought to be due to Nrf2 induction. The trial on this drug had to be stopped due to adverse events including 57 deaths out of 2185 trail participants. The inducer activity of this drug compared to sulforafance when studying a range of triterpenoids showed it to be 230 fold more potent than sulforafane as a NQO1 inducer. (Christine A. Houghton, 2016) The amount of triterpenoids produced by foods are considered to be non-toxic. The amount in Bardoxolone Methyl appears to be toxic. The researchers are assuming the issue with the oleanolic acid was simply due to the increased dose, but I also am aware that it is not a natural substance, and it is given out of context of all the other lovely accompanying substances that are in the foods rich in oleanolic acid.

 

Inhibitors

• Both Phase I and Phase II can be inhibited.
• Enzymes do not work well if there is a lack of active substrate, or if they lack cofactors, or if they are exposed to excessive toxic, or chronic sources of compounds such as heavy metals, solvents, chemicals, or toxins.
• When there is more than one compound that is transformed by a single enzyme, there is what is called competitive inhibition. In this case one compound is unable to be transformed due to the competition of the other compound.
• An increase in toxins can also lead to what is called inhibition due to increased toxic load. It is simply a case of using up available enzymes faster than they can be made.

 

When To Suspect Toxicity Issue In Patient

• History of increasing sensitivity to exogenous exposures.
• Abundant use of medications and or supplements
• Paradoxical responses, or sensitivity to medications, or supplements
• Significant past or present use of toxic chemicals in home, work or environment
• Sensitivity to odors
• Trouble going into new buildings or buildings with a lot of new products
• Musculoskeletal symptoms such as fibromyalgia
• Inflammatory disorders
• Cognitive dysfunction
• Autonomic dysfunction
• Worsening of symptoms after anesthesia or pregnancy

 

General Biotransformation/Detoxification Support

• Remove offending toxins/foods/drugs/heavy metals.
• Remove environmental exposures in home, or work, or remove the person from the environment.
• Air filters
• Water filters
• Hepa filters on vacuums
• Remove or modulate any out of control organisms
  • Bacterial
  • Parasitic
  • Viral
  • Fungal
• Support Organs Of Elimination As Needed
• Ingest necessary nutrients, clean water (stay suficiently hydrated), clean air, only organic food, including organic meat
• Provide increased nutrients that function as cofactors, or are required in enzymatic steps of the biotransformational/detox pathways
• Focus on vegetables high in minerals and healthy polyphenols
• Get adequate sun, rest/sleep and use meditation/prayer daily
• Clean and monitor heating and air conditioning systems in home, work and car.
• Do not wear dry cleaned clothing.
• Beaware of toxic household cleaners, garden chemicals, personal care products, cooking pots, food storage containers, do not use dryer sheets.
• Stay away from car exhaust and cigarette smoke
• Minimize electromagnetic radiation from radios, T.V.s, phones, computers etc.
• Decrease ionizing radiation from medical tests such as x-rays.
• Reduce heavy metal exposure from larger predatory fish, water, lead paint, mercury fillings in teeth, thimerosal-containing products.
• Consider chelation, infrared saunas, or steam saunas, bile sequestrants, and antioxidants, to reduce the toxic load.
• Examine genetic polymorphisms that may make them more susceptible. A single nucleotide polymorphism (SNP) can change an amino acid in the protein coding sequence, and thereby alter an enzyme binding site and/or the substrate binding site, which may affect the overall function. Genetic polymorphisms in biotransformation/detox may play a significant role in the pathophysiology of certain diseases.

 

Links To Additional Articles On The Detox/Biotransformation System

For a more in-depth overview of the detox/biotransformation system of the body,  including the cytochrome P450 system, glutathione conjugation, amino acid conjugation, methylation, sulfation, acetylation and glucuronidation, as well as information on testing of these systems, check out the article, "Detox & Biotransformation System Overview."

If you are looking for data on individual biotransformation pathways, the links to each pathway can be found at Detox/Biotransformation Pathways

For information on how these biotransformation systems are supported in see the article "Supporting The Detox - Biotransformation System in mold related illness (other toxins too)".

 

Terminology

Endogenous: Produced originating inside of the organism.

Exogenous: Produced or originating outside of the organism.

Ferritin: Binding of free iron to prevent its reaction with superoxide to produce hydroxyl radical.

Glutathione: A predominant intracellular sulfur-containing direct antioxidant. Essential in function of Glutathione peroxidase and reduced glutathione for redox balance and detoxification.

Glutathione-S-transferase: A Phase II detoxifying enzyme with broad spectrum of activity, depending on subclass. Best known for catalyzing conjugation of the reduced form of glutathione to xenobiotics for removal from the body.

Hemoxygenase-1: Redox-regulating, broad protection against oxidative stress.  Metabolises haem, also producing bilirubin which scavenges peroxyl radicals.  Anti-inflammatory and immune-modulating properties.

Metallothionein: Helps removal of heavy metals such as mercury and cadmium.

NADPH regenerative enzymes: Restores reducing equivalents and reduces oxidized GSH to its reduced form.

Nuclear factor erythroid 2-related factor 2: Nrf2 induces its own synthesis. It can be inuced by many substances.

Peroxisome proliferator-activated receptor: Regulator of adipogenesis and central integrator of glucose metabolism, energy homeostasis and skeletal metabolism.

Quinone oxidoreductase - NAD(P)H:Quinone oxido-reductase has a protective function for cells against the toxicity of electrophiles and reactive forms of oxygen. In addition, its induction protects cells against carcinogenesis. Therefore, quinone reductase is acknowledged as belonging to the group of enzymes classified as phase 2 detoxification enzymes.

Quinone oxidoreductase catalyzes the beneficial two-electron reduction of quinones to hydroquinones, preventing the one-electron reduction of quinones by other quinone reductases that would result in the production of radical species.

A multifunctional redox-regulating and detoxifying enzyme, including protection against oestrogen quinone metabolites. Directly scavenges superoxide but less efficiently than SOD.  Stabilises the p53 tumor suppressor protein, especially under exposure from γ-irradiation or other oxidative stress. Protective against dopamine cytotoxicity where SOD and Catalase were not. Upregulation of its activity by Nrf2 induction is described as an avenue for maintaining cellular defenses with advancing age.

Thioredoxin (non-enzyme): Ubiquitous intracellular sulfur-rich protein. Singlet oxygen quencher and hydroxyl radical scavenger.

Thioredoxin reductase: An oxido-reductase which regenerates thioredoxin and GSH.

Xenobiotic: In relattion to the human or animal body, a xenobiotic is a foregin compound that originates externally to the body in sources such as environmental toxins or drugs.

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