DETOX: Fact Versus Fiction

Whether it’s cucumbers splashing into water or models sitting smugly next to a pile of vegetables, it’s tough not to be sucked in by the detox industry. The idea that you can wash away your calorific sins is the perfect antidote to our fast-food lifestyles and alcohol-lubricated social lives. But before you dust off that juicer or take the first tentative steps towards a colonic irrigation clinic, there’s something you should know: detoxing – the idea that you can flush your system of impurities and leave your organs squeaky clean and raring to go – is a scam. It’s a pseudo-medical concept designed to sell you things.

What is detox?

Before it was co-opted in the recent craze, the word "detox" referred chiefly to a medical procedure that rids the body of dangerous, often life-threatening, levels of alcohol, drugs, or poisons. Patients undergoing medical detoxification are usually treated in hospitals or clinics. The treatment generally involves the use of drugs and other therapies in a combination that depends on the type and severity of the toxicity.

The detox programs now being promoted to the health-conscious public are a different matter. These are largely do-it-yourself procedures aimed at eliminating alleged toxins that are held responsible for a variety of symptoms, including headache, bloating, joint pain, fatigue, and depression. Detox products are not available by prescription; they are sold in retail stores, at spas, over the Internet, and by direct mail. Many are advertised as useful for detoxifying specific organs or systems; others are portrayed as "whole body" cleansers. 

Let's be clear:If toxins did build up in a way your body couldn’t excrete, you’d likely be dead or in need of serious medical intervention. The healthy body has kidneys, a liver, skin, even lungs that are detoxifying as we speak. There is no known way – certainly not through detox treatments – to make something that works perfectly well in a healthy body work better.

Our body has an amazing capacity to rid itself of harmful substances! We take in toxins daily through eating natural plant toxins and man-made chemicals, through breathing in air pollution, and through slathering on skin care products.

 Our detoxification genes panel help you to understand how your own genes for detoxification can help you prioritize which toxins are the worst for you and which drugs to avoid.

Why is this so important?

The rate that a medication or supplement is metabolized affects how well your body will react to that drug — too fast and you may not get the effect needed; too slow and you may build up too much in your body when you take the next dose. Doctors often say “try this medication and see how it works for you”. Knowing how your genes work, you can skip part of the “try this” and know what is more likely to work.

The detoxification process can be roughly divided into three phases: Phase I is governed by transformation enzymes – these enzymes oxidize, reduce and hydrolyze toxins/drugs

·      Phase II is managed by conjugation enzymes – these enzymes conjugate Phase I products

·      Phase III is carried out by transport proteins – these proteins transport the final products from the cell

Phase I detoxification

A lot of toxins – whether eaten, breathed, or created in our bodies – are broken down by the Cytochrome P450 family of enzymes in what is known as phase I of detoxification. Most of this takes place in the liver, which is the body’s main organ for detoxification.

A simplified explanation…. CYP450 is a group term for the enzymes that take a substance (xenobiotics or endogenous) and breaks it into metabolites, or smaller substances. CYP450 enzymes have iron and oxygen in them, and through a redox reaction can make a drug more polar. Polar molecules are more hydrophilic (likes water) and are able to be eliminated through the kidneys.

For each variant that speeds up or slows down drug metabolism, you should read up on any pharmaceutical medications that are broken down by that gene/enzyme.

CYP1A1 – This enzyme detoxifies polycyclic aromatic hydrocarbons such as exhaust fumes and charbroiled meats. Mine sucks – I have a 70-90% reduction in this enxyme. CYP1A1 converts estrogens to 2-hydroxyestrogens, which are protective against breast cancer if methylated, but which may be carcinogenic if not. CYP1A1 also activates many environmental xenobiotics to pro-carcinogenic intermediates. A CYP1A1 polymorphism is associated with increased CYP1A1 enzyme activity. Whereas the polymorphism MspI variant has been associated with both decreased and increased risk (in smokers) of breast cancer, the I462V variant has been linked in several studies with increased risk of cancer, especially in smokers and women exposed to PCBs.

CYP1B1 – Important guy for the 4-hydroxylation of estrogen; that is, CYP1B1 takes your garden-variety estrogen and converts it to 4-hydroxyestrogen. 4-hydroxyestrogen is a potent estrogen that may, in turn, be oxidized to carcinogenic compounds. A polymorphism is associated with increased enzyme activity, therefore increased production of these potentially harmful metabolites.

CYP2A6 – Detoxifies nitrosamines and nicotine. Nitrosamines are chemicals that arise from certain reactions such as making bacon, and some of them are carcinogenic.

CYP1A2 –  Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.Metabolism of Cymbalta, Welbutrin

CYP2C19 is involved with the metabolism of multiple medications. The most common are diazepam, omeprazole, and sertraline. Cyp2c19 also metabolizes progesterone.  There are two major variants that result in loss of activity. These are Cyp2C19*2 and Cyp2C19*3.

CYP2D6 is involved with the metabolism of about 20% of drugs on the market. It also metabolizes serotonin and neurosteroids. There are five different polymorphisms that can lead to decreased activity. Some of the classes of drugs that are metabolized by Cyp2D6 are antidepressants, SSRIs, opioids, and antipsychotics. 

CYP2E1 is involved with the detoxification of many industrial pollutants, as well as carcinogens. Cyp2e1 also metabolizes ethanol to acetaldehyde and acetate. Cyp2e1 is also responsible for bioactivating a number of carcinogens, including cigarette smoke. 

CYP3A4 is responsible for metabolizing more compounds than most other P450s. It is responsible for metabolizing sex hormones, caffeine, statins, SSRIs, antifungals, antidepressants, and many other medications. Some antibiotics can negatively affect its activity. Also, grapefruit and pomegranate juice have been shown to be potent inhibitors. 

CYP2C9– metabolism of warfarin, Crestor, celecoxib, and more

CYP2E1 – metabolism of fatty acids, alcohol, and some aesthetics

Phase II detoxification

Phase 2 enzymes traditionally refer to the enzymes catalyzing the conjugation reactions, such as glutathione S-Transferase (GST) , UDP-glucuronosyltransferase (UGT) , N-acetyltransferase (NAT), and  sulfotransferase.

DetoxGenes phase II

UGT

GST

NAT

NAT2, 1 N-acetyltransferase 1 is found in extra-hepatic tissues, while NAT2 is found predominantly in the liver and the gut. Both are used in the Phase II acetylation of numerous environmental toxins, including heterocyclic aromatic amines. Slow acetylators do not clear toxins well and the resulting increased total toxic burden can increase the risk of lung, colon, breast, bladder, and head and neck cancers, though results have not been consistent in all studies. Urinary bladder cancer appears to have the most consistent association with slow acetylation. Rapid acetylators increase O-acetylation of toxins that can actually make the toxins more reactive. These transformed toxins may increase risk of developing lung, colon, breast, bladder, head and neck cancer, though results have not been consistent in all studies. Colon cancer appears to have the most consistently reproducible association with fast acetylation.

Glutathione S-transferases (GST) are responsible for detoxifying certain products of oxidative stress and a variety of electrophilic xenobiotics and carcinogens such as solvents, herbicides, pesticides, polycyclic aromatic hydrocarbons, steroids, and heavy metals. GSTM1 is located primarily in the liver, whereas GSTP1 is located primarily in the brain and lungs. When there is no gene present on the GSTM1 chromosome it is called an "absent" allele. This results in reduced capacity for hepatic detoxification and increased risk of various cancers, chemical sensitivity, coronary artery disease in smokers, atopic asthma, and deficits in lung function. Risk appears reduced for colorectal- and head & neck cancer, but only when cruciferous vegetable intake is high. GSTP1 polymorphisms are associated with either higher or lower enzyme activity, depending on the exposure. This GSTP1 polymorphism is associated with increased risk of various cancers, risk that is compounded by exposure to cigarette smoke and the "absent" GSTM1.

Glucuronosyltransferases are responsible for the process of glucuronidation a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s.

The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. UGT is present in humans, other animals, plants, and bacteria. Famously, UGT enzymes are not present in the genus Felis,[3] and this accounts for a number of unusual toxicities in the cat family.

Diseases: A deficiency in the bilirubin specific form of glucuronosyltransferase is thought to be the cause of  Gilbert’s syndrome which is characterized by unconjugated hyperbilirubinemia

 It is also associated with Crigler Najjar Syndrome a more serious disorder where the enzyme's activity is either completely absent (Crigler-Najjar syndrome type I) or less than 10% of normal (type II).

Infants may have a developmental deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol lwhich requires glucuronidation. This leads to a condition known as Gray baby syndrome.

Phase III of detoxification is responsible for eliminating toxins and metabolic products from cells.

Phase III transporters can be found in the liver, intestine, kidney and brain, where they act as a barrier against drug entry, and manage endobiotic and xenobiotic absorption, distribution and excretion.

The bottom line

The human body can defend itself very well against most environmental insults and the effects of occasional indulgence (see "The body's own detox system"). If you're generally healthy, concentrate on giving your body what it needs to maintain its robust self-cleaning system — a healthful diet, adequate fluid intake, regular exercise, sufficient sleep, and all recommended medical check-ups. If you experience fatigue, pallor, unexplained weight gain or loss, changes in bowel function, or breathing difficulties that persist for days or weeks, visit your doctor instead of a detox spa.

And check your detox genes!