The Science of Detoxification: How Phase I Relates to Health

Detoxification Part III: The Process of Detoxification

The Science of Detoxification: How Phase I Relates to Health

Mary’s exam was striking but not unusual. Her hands and feet were cold and her nails had significant ridging and were brittle.

Her tongue was red and slightly enlarged for her mouth causing small scallops along its edge and I noted an unusual, foul smell to her breath. Her liver was a little tender on exam as well, though not especially enlarged.

Finally, her skin had an overall dusky and mottled appearance. Per her account, all of these findings began to arise five years ago.

What changes in Mary’s diet had led up to her physical and circulatory changes? Which of her past chemical and environmental exposures were contributing to her current condition? Could her sluggish bowel movements and poor urine production be augmented? Could I design a plan to assist her body in it’s ability to remove the toxins she has built up over all these years?

In Part III, I’d to review how our body goes about the process of detoxification in order to help the reader know how to better augment and assist this natural process.

There are four major processes our body must perform to remove toxins:

The liver serves as a major filter for all of the blood coming from the large and small intestines. This blood is exposed to the cells of the liver which possess enzymes to detoxify the contents of the blood.

The process of detoxification results in the production of bile that is then secreted into the small intestines. But prior to its excretion, the toxins in the bile have to be processed at the cellular level.

Phase I and Phase II detoxification occurs at the level of the cells in the liver.

Phase I & II Detoxification

Phase I detoxification is the process by which reactive metabolites naturally made in the body and toxins that enter the body are for elimination by making them more water soluble.

However, in this process of becoming more water soluble they also become more reactive and thus have an increased potential for harm.

Phase II detoxification then takes these intermediaries, makes them less reactive, tags them for elimination by the liver cells into the bile and then they are excreted into the stool as bile and eventually the body.

The liver is one the major locations for this process to occur in the body, but it also occurs in the kidney and bacteria in the GI tract (both sometimes called Phase III detoxification).

For the kidneys to optimally perform their Phase I and II detoxification duties, they require adequate blood pressure (through hydration with pure clean water) and minerals in addition to alkalizing substances. What this means is that if you don’t drink enough clean water, it will impede your body’s ability to excrete toxins through your kidneys.

Also, if you don’t get enough of the nutrients listed in the Phase I detoxification column, your kidneys won’t work optimally. This requires eating lots of green vegetables, citrus, and mineral dense foods bone broth.

Akalinization is a term often thrown around and often used incorrectly. It doesn’t mean you should drink soda water or eat tums (or drink alkalinizing water) but eat/drink substances that enable your kidneys to do their job, create relative alkalinity (pH >6.4), and expel toxins into the urine for elimination from the body. We will discuss the specifics of how to do this in Part IV.

Your gastrointestinal tract houses over 100 trillion bacteria that interact with the foods we eat and the secretions of our intestinal lining as well as those of the liver and pancreas.

This interaction includes interacting with toxins excreted by the liver and those toxins in the unabsorbed food we eat.

I could write a whole series on this, but fortunately I don’t have to, Chris Kresser has already done a nice job of this, so for the sake of time and space I’ll refer to his well-written article on this topic.

So, in the few paragraphs above, we discover the need for:

  • Clean, fresh, nutrient-dense food
  • Adequate hydration

Breathing is typically less thought of as a detoxification process, but if you were to stop expiring the carbon dioxide that your cells make during cell metabolism, you would die within minutes.

Because this process is so natural and occurs literally without thought, it is often overlooked. Also breathing in—inspiration—is a potential source for toxin exposure.

This is an area we all need to think about.

Air pollution can be a source for lung inflammation and respiratory disease as well as cancer. Autoimmune diseases rheumatoid arthritis and even Alzheimer’s Disease have been associated with air pollution. The above links are great resources to learn more concerning this field of medical research.

In Part IV we will discuss ways to improve the air quality of your home and minimize this risk. For our purposes here, the basic concept is that you need clean fresh air just as much as you need clean fresh water.

And just as easily as we breath out and eliminated carbon dioxide made in our bodies, if the air is full of pollutants, we can breathe these into our lungs and they can enter our bodies.

Does anyone actually sweat these days? Hardly anyone has an outside job; we live in air-conditioned environments; even our gyms are conditioned for our comfort. The result is that even in work out places it’s hard to get a good sweat.

This area of detoxification seems fairly intuitive; we all sweat large amounts prior to the age of air conditioning and today most of us don’t sweat enough. However, this is a controversial area because there isn’t a lot of direct research in the area.

So, we will have to look at it indirectly.

First, there are substances, especially Persistent Organic Pollutants (POPs) that are preferentially excreted via perspiration. Heavy metals mercury, lead and cadmium are also excreted more in sweat than in urine.

Since we don’t know exactly how this process works, the most interesting data to me is the scientific use of Far Infra Red Saunas to treat first responders for toxin exposures. FAR-IR is an invisible form of infra-red light that heats a person’s body and makes them sweat.

The technology is relatively inexpensive and a unit can be purchased at Costco (or Craig’s List for used ones). There are multiple studies looking at high exposure individuals (usually first responders or industrial workers).

In these studies, the patients had severe symptoms ranging from chronic fatigue and pain to respiratory tracts diseases and hormone imbalances. The levels of certain chemicals were measured then the patients were treated with FAR-IR.

The improvements in their health were spectacular and the mechanism for this, from the studies, was the detoxifying effect of the FAR-IR. The current research is compelling, but more research is needed.

I never learned in medical school about the health benefits or detoxifying effects of FAR-IR because we didn’t even know about it in 1996. Today we are just beginning to scratch the surface of this field. Interestingly though, in ancient healing traditions (e.g. Mayan’s in CA, TCM in China or Ayurveda in India), sweating was commonly used to help detoxify the body and maintain balance. Ultimately FAR-IR is safe and effective, even if we don’t know all the ways in which it may be having its effect.

Defecation, urination, perspiration and expiration: the four major ways our body eliminates both metabolic toxins and environmental toxins we are exposed to. You may say this is all great info, but what now. Is this actionable data or just knowledge for the sake of knowledge?

In Part IV, I will present a complete detoxification program that will address all of the topics discussed in the previous three parts.


The Science of Detoxification: How Phase I Relates to Health

The Science of Detoxification: How Phase I Relates to Health

The human body has an amazingly efficient detoxification system, mostly located in the liver. In healthy people, these detoxification processes are in balance, and most of the time function well.

However, some diseases, vitamin deficiency, exposure to tobacco smoke, alcohol, and drugs may upset the balance between detoxification enzymes. This post will focus on phase I: the first step to removing toxins from the body.

We’ve also compiled a list of natural factors that may increase or decrease the activity of CYPs, a big family of phase I enzymes.

Basic Mechanisms at Work

Modern life is the use of chemicals. The current count of individual substances is now approaching 100 million, and humans and other species are exposed to a great number of them [1].

Our bodies process and remove these foreign chemicals (xenobiotics) thanks to our efficient detoxification mechanisms. These mechanisms also deal with metabolic products such as excess hormones (endobiotics).

Xenobiotic metabolism usually converts fat-soluble compounds into more water-soluble derivatives that can be easily eliminated from the body [1].

“Enzymes of detoxification” are a big family of enzymes that participate in altering xenobiotics (i.e. foreign compounds), so as to make them either more readily excretable or less pharmacologically active [2].

Detox Phases

The detoxification process can be roughly divided into three phases [3]:

  • 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

Phases I, II, and III must work in unison for the proper removal of unwanted toxins, drugs, and excess hormones.

These enzymes have broad substrate ranges. They are relatively more concentrated at major points of entry to either the body (liver, lung, intestinal mucosa) or a specific organ (the choroid plexus for the brain). Many also appear to be inducible, i.e. the body responds to exposure to a certain toxin by producing more of the enzyme that degrades it [2].

Detox Organs

The liver is the primary detoxification organ, as it filters blood coming directly from the intestines and prepares toxins for excretion from the body [1].

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 [1].

The enzymes of detoxification are slow compared to other enzymes, but they are present in very large amounts. For example, Phase II glutathione transferases represent 10% of the total protein in the liver [2].

Enzymatic Transformation Makes Toxins More Soluble

Phase I enzymes begin the detoxification process by chemically transforming fat-soluble compounds into water-soluble compounds. Water-soluble compounds can easily be excreted, while fat-soluble compounds can be stored in fat cells, where they are protected from the body’s detoxification enzymes [4].

Phase I reactions include oxidation, reduction, hydrolysis and cyclization [4].

These reactions are mediated by [1, 5, 6, 7, 8]:

  • The versatile cytochrome P450 (CYP) enzymes
  • The more selective flavin-containing monooxygenases (FMOs, responsible for the detoxification of nicotine from cigarette smoke)
  • Monoamine oxidases (MAOs, which break down serotonin, dopamine, and epinephrine in neurons)
  • Alcohol and aldehyde dehydrogenases (which metabolize alcohol)
  • Epoxide hydrolases (EH), and
  • Other phase I enzymes.

Cytochrome P450 monooxygenases (CYPs)

Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body [9].

CYPs metabolize polycyclic aromatic hydrocarbons, aromatic amines, heterocyclic amines, pesticides, and herbicides, and the vast majority of other drugs [1].

However, CYPs also metabolize endogenous biochemicals (for example, CYP19A1, also called aromatase, transforms testosterone to estradiol) [10].

The Human Genome Project identified 57 human CYPs [4]. However, about 12 hepatic CYPs are responsible for the metabolism of the majority of drugs and other xenobiotics (approximately 93% of the drug metabolism) [1, 4].

Among them, CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19 are responsible for nearly 60% of the drug metabolism [4].

Note that although CYPs are detoxification enzymes, these reactions often convert less toxic molecules into more toxic active products. That is where the phase II detoxification steps in.

For example, CYP1A1 can activate some carcinogens [11, 12] while CYP2E1 can activate several liver toxins and contribute to alcoholic liver damage [13].

We differ in our CYPs

More than 2,000 mutations in CYP genes have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity [4].

Genetic polymorphisms, which were shown to depend on ethnicity, play a major role in the function of CYPs (especially CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP2A6), and lead to distinct pharmacogenetic phenotypes termed as poor, intermediate, extensive, and ultrarapid metabolizers [14].

Polymorphisms in CYP1A1, CYP1A2, CYP2C8, CYP2E1, CYP2J2, and CYP3A4 are generally less predictive, but data show that predictive variants exist [14].

Individuals in a population can be stratified according to metabolic ratios of particular CYPs. For example, the most frequent phenotype of CYP2D6 is extensive-metabolizer (78.8%). In other words, 78.8% of us are extensive metabolizers. This group is followed by intermediate- (12.1%), poor (7.6%) and ultra-rapid metabolizers (1.5%) [4].

Research suggests that, for example, a CYP2D6 poor metabolizer should not be administered codeine since the drug would have no effect. Conversely, a CYP2D6 ultra-rapid metabolizer would ly suffer side effects from a normal dosage [4].

In one study, a polymorphism in CYP2C19, CYP2C192, was associated with a 30% increased risk of major adverse cardiovascular events during treatment with clopidogrel. On the other hand, CYP2C1917 was linked with an increased risk of bleeding during clopidogrel therapy [4].

Nonetheless, more clinical research is needed before doctors can modify drug dosage each person’s CYP activity.

Factors that Influence CYPs (Sex, Age, Diet, Health)

The figure above shows the proportion of drugs metabolized by CYP enzymes. Important variability factors are indicated by bold type with possible directions of influence indicated by arrows. Factors of controversial significance are shown in parentheses [15].

Sex: Most clinical studies indicate that women metabolize drugs more quickly than men. This is particularly the case with the major drug-metabolizing CYP3A4. Analyses have shown ~2-fold higher levels of CYP3A4 protein in female compared to male liver tissue [15].

Age: Studies in the human liver suggest a modest increase in expression and activity of most CYPs during life, particularly CYP2C9 [15].

Disease: Evidence suggests that disease states generally have a negative effect on drug metabolism capacity. During infection, inflammation, and cancer, circulating proinflammatory cytokines – such as IL-1β, TNF-α, and IL-6 – seem to lead to severe downregulation of many drug-metabolizing enzymes [15].

Patients with chronic kidney disease (CKD) have reduced cytochrome P450 (CYP) enzyme activity [16].

On the other hand, CYP2E1 is upregulated in diabetes and may contribute to the ongoing cellular damage observed in diabetes and obesity, according to some researchers [17].

Diet: According to limited research, protein deficiency inhibits, while protein-rich diet increases CYP activity [18]. A high-carbohydrate diet was shown to decrease CYP activity in one older study, but present-day studies would need to confirm this link [19].

On the other hand, a diet high in saturated fats was suggested to activate CYP2E1, the enzyme that was shown to be upregulated in diabetes [17].

A Word of Caution

Altered (increased or decreased) CYP activity underlies most drug interactions.

It’s one of the reasons why supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Remember, CYP enzymes metabolize most drugs.

Theoretically, all substances that lower CYP activity may slow the metabolism of drugs and increase their blood levels. This may lead to an increased risk of toxicity or serious side effects.

On the other hand, substances that increase CYP activity may speed up the metabolism and removal of drugs. This can reduce the drug’s blood levels and make it less effective.

Always consult your doctor before supplementing or making any major changes to your diet or lifestyle. It’s important to let them know about all drugs and supplements you are using or considering.

Additionally, have in mind that detox supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Herbs, Foods, and Other Compounds

Many of the effects described below have only been studied in animals or cells. For nutrients lacking clinical data, CYP interactions in humans are unknown.

  • Compounds found in grapefruit juice and some other fruit juices (including bergamottin, dihydroxybergamottin, and paradicin-A) have been found to inhibit CYP3A4, leading to increased bioavailability of CYP3A4-mediated drugs. These compounds thus increase the possibility of overdosing [20].
  • Starfruit juice inhibits CYP2A6, CYP1A2, CYP2D6, CYP2E1, CYP2C8, CYP2C9 and CYP3A4 [21].
  • Watercress inhibits CYP2E1, which may result in altered drug metabolism for individuals on certain medications (e.g., chlorzoxazone) [22].
  • Goldenseal, with its two notable alkaloids berberine and hydrastine, has been shown to inhibit CYP2C9, CYP2D6, and CYP3A4 [23, 24].
  • Eurycoma longifolia, Labisia pumila, Echinacea purpurea, Andrographis paniculata, and Ginkgo biloba inhibit CYP2C8 [25].
  • Propolis inhibits CYP1A2, CYP2E1, and CYP2C19 [26].
  • Lycopene, a red pigment found in tomatoes, carrots, and watermelon, inhibits CYP1A1 and CYP1B1 [27].
  • Licochalcone A, a major compound in traditional Chinese herbal licorice, significantly inhibits CYP1A2, CYP2C19, CYP2C8, CYP2C9, and CYP3A4 and exhibits weak inhibitory effects on CYP2E1 and CYP2D6 [28].
  • Caffeic acid and quercetin, commonly found in plants, potently inhibit CYP1A2 and CYP2C9. Caffeic acid further inhibits CYP2D6 and weakly inhibits CYP2C19 and CYP3A4. Quercetin potently inhibits CYP2C19 and CYP3A4 and moderate inhibits CYP2D6 [29].
  • Ginger extract inhibits CYP2C19 [30].
  • Kale ingestion, un that of other cruciferous vegetables, may inhibit CYP3A4, CYP1A2, CYP2D6, and CYP2C19 [31].
  • Piperine, a constituent of black pepper, decreases CYP3A4 [17].
  • Oleuropein, derived from olive oil, inactivates CYP3A4 and slightly inhibits CYP1A2 [17].
  • Garlic inhibits CYP2E1 [32].
  • Resveratrol and garden cress inhibit CYP3A4 [32].
  • Berries and their constituent ellagic acid may reduce CYP1A1 overactivity [32].
  • Apiaceous vegetables may attenuate excessive CYP1A2 action [32].
  • Chrysoeriol, present in rooibos tea and celery, may inhibit CYP1B1 [32].
  • N-acetyl cysteine, ellagic acid, green tea, black tea, dandelion, chrysin, and medium chain triglycerides (MCTs) may downregulate CYP2E1 [32].
  • Saint-John’s wort decreases CYP1A1, CYP1B1, and CYP2D6 [33].

Herbs and Foods

  • Common valerian increased the activity of CYP3A4 and 2D6 [34].
  • Ginkgo biloba increased the activity of CYP1A2 and CYP2D6 [34].
  • Broccoli and cruciferous vegetables induce CYP1A1/1A2 [32].
  • Resveratrol and resveratrol-containing foods enhance CYP1A1 [32].
  • Curcumin may upregulate 3A4 activity [32].
  • Rooibos tea, garlic, and fish oil appear to induce the activity of CYP3A, 3A1, and 3A2 [32].
  • Saint-John’s wort can increase CYP3A4 [35, 36].


  • 17β-estradiol (E2) at high concentrations reached during pregnancy, increases CYP2B6 expression [38].

Note that many foods appear to act as both inducers and inhibitors of CYP enzymes, their concentration or composition (curcumin/turmeric, black tea/ theaflavins, soybean) [32]. while other foods increase particular CYP enzymes while decreasing others.

It is also important to know that elevated Phase I activity is not always a good thing. As Phase I enzymes produce toxic and carcinogenic compounds, you want them to be in balance with Phase II enzymes.

Receptors that Activate CYP enzymes

The expression of phase I genes is governed by a number of nuclear receptors, including aryl hydrocarbon receptors (AhR), PPARα and orphan nuclear receptors such as constitutive androstane receptors (CAR) and pregnane X receptors (PXR) [3, 17].

These receptor interactions are highly experimental and proper human data are lacking:

  • Polycyclic aromatic hydrocarbons (PAHs) activate Ahr, which in turn increases CYP1A and CYP1B enzymes [17]. This is an example where CYPs 1A and 1B oxidize PAH and aromatic amines to carcinogenic products [17].
  • PXR binds small molecules such as steroids, rifampicin, and metyrapone, and increases CYP3A [17].
  • CAR binds phenobarbital, orphenadrine and other drugs that activate CYP2B [17].
  • Clofibrate and other chemical peroxisome proliferators activate PPARα, thereby inducing CYP4A [17].

Learn More


You can’t detox your body. It’s a myth. So how do you get healthy?

The Science of Detoxification: How Phase I Relates to Health

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.

“Let’s be clear,” says Edzard Ernst, emeritus professor of complementary medicine at Exeter University, “there are two types of detox: one is respectable and the other isn’t.

” The respectable one, he says, is the medical treatment of people with life-threatening drug addictions.

“The other is the word being hijacked by entrepreneurs, quacks and charlatans to sell a bogus treatment that allegedly detoxifies your body of toxins you’re supposed to have accumulated.”

If toxins did build up in a way your body couldn’t excrete, he says, you’d ly 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,” he says. “There is no known way – certainly not through detox treatments – to make something that works perfectly well in a healthy body work better.”

With celebrity advocates from Gwyneth Paltrow to Oprah Winfrey, detoxing has become big business.Rich Peppiatt thinks he’s found the solution to our detoxing obsession … and it tastes a bit liquified animal.

Much of the sales patter revolves around “toxins”: poisonous substances that you ingest or inhale. But it’s not clear exactly what these toxins are. If they were named they could be measured before and after treatment to test effectiveness. Yet, much floaters in your eye, try to focus on these toxins and they scamper from view.

In 2009, a network of scientists assembled by the UK charity Sense about Science contacted the manufacturers of 15 products sold in pharmacies and supermarkets that claimed to detoxify. The products ranged from dietary supplements to smoothies and shampoos.

When the scientists asked for evidence behind the claims, not one of the manufacturers could define what they meant by detoxification, let alone name the toxins.

Yet, inexplicably, the shelves of health food stores are still packed with products bearing the word “detox” – it’s the marketing equivalent of drawing go-faster stripes on your car.

You can buy detoxifying tablets, tinctures, tea bags, face masks, bath salts, hair brushes, shampoos, body gels and even hair straighteners. Yoga, luxury retreats, and massages will also all erroneously promise to detoxify.

You can go on a seven-day detox diet and you’ll probably lose weight, but that’s nothing to do with toxins, it’s because you would have starved yourself for a week.

Then there’s colonic irrigation. Its proponents will tell you that mischievous plaques of impacted poo can lurk in your colon for months or years and pump disease-causing toxins back into your system.

Pay them a small fee, though, and they’ll insert a hose up your bottom and wash them all away.

Unfortunately for them – and possibly fortunately for you – no doctor has ever seen one of these mythical plaques, and many warn against having the procedure done, saying that it can perforate your bowel.

Other tactics are more insidious.

Some colon-cleansing tablets contain a polymerising agent that turns your faeces into something a plastic, so that when a massive rubbery poo snake slithers into your toilet you can stare back at it and feel vindicated in your purchase.

Detoxing foot pads turn brown overnight with what manufacturers claim is toxic sludge drawn from your body. This sludge is nothing of the sort – a substance in the pads turns brown when it mixes with water from your sweat.

“It’s a scandal,” fumes Ernst. “It’s criminal exploitation of the gullible man on the street and it sort of keys into something that we all would love to have – a simple remedy that frees us of our sins, so to speak. It’s nice to think that it could exist but unfortunately it doesn’t.”

Spinach and broccoli smoothie.

That the concept of detoxification is so nebulous might be why it has evaded public suspicion. When most of us utter the word detox, it’s usually when we’re bleary eyed and stumbling the wrong end of a heavy weekend.

In this case, surely, a detox from alcohol is a good thing? “It’s definitely good to have non-alcohol days as part of your lifestyle,” says Catherine Collins, an NHS dietitian at St George’s Hospital. “It’ll probably give you a chance to reassess your drinking habits if you’re drinking too much.

But the idea that your liver somehow needs to be ‘cleansed’ is ridiculous.”

The liver breaks down alcohol in a two-step process. Enzymes in the liver first convert alcohol to acetaldehyde, a very toxic substance that damages liver cells. It is then almost immediately converted into carbon dioxide and water which the body gets rid of.

Drinking too much can overwhelm these enzymes and the acetaldehyde buildup will lead to liver damage. Moderate and occasional drinking, though, might have a protective effect.

Population studies, says Collins, have shown that teetotallers and those who drink alcohol excessively have a shorter life expectancy than people who drink moderately and in small amounts.

“We know that a little bit of alcohol seems to be helpful,” she says.

“Maybe because its sedative effect relaxes you slightly or because it keeps the liver primed with these detoxifying enzymes to help deal with other toxins you’ve consumed.

That’s why the government guidelines don’t say, ‘Don’t drink’; they say, ‘OK drink, but only modestly.’ It’s a little of what doesn’t kill you cures you.”

This adage also applies in an unexpected place – to broccoli, the luvvie of the high-street “superfood” detox salad.

Broccoli does help the liver out but, un the broad-shouldered, cape-wearing image that its superfood moniker suggests, it is no hero. Broccoli, as with all brassicas – sprouts, mustard plants, cabbages – contains cyanide.

Eating it provides a tiny bit of poison that, alcohol, primes the enzymes in your liver to deal better with any other poisons.

Collins guffaws at the notion of superfoods. “Most people think that you should restrict or pay particular attention to certain food groups, but this is totally not the case,” she says. “The ultimate lifestyle ‘detox’ is not smoking, exercising and enjoying a healthy balanced diet the Mediterranean diet.”

Close your eyes, if you will, and imagine a Mediterranean diet. A red chequered table cloth adorned with meats, fish, olive oil, cheeses, salads, wholegrain cereals, nuts and fruits. All these foods give the protein, amino acids, unsaturated fats, fibre, starches, vitamins and minerals to keep the body – and your immune system, the biggest protector from ill-health – functioning perfectly.

So why, then, with such a feast available on doctor’s orders, do we feel the need to punish ourselves to be healthy? Are we hard-wired to want to detox, given that many of the oldest religions practise fasting and purification? Has the scientific awakening shunted bad spirits to the periphery and replaced them with environmental toxins that we think we have to purge ourselves of?

Susan Marchant-Haycox, a London psychologist, doesn’t think so. “Trying to tie detoxing in with ancient religious practices is clutching at straws,” she says.

“You need to look at our social makeup over the very recent past.

In the 70s, you had all these gyms popping up, and from there we’ve had the proliferation of the beauty and diet industry with people becoming more aware of certain food groups and so on.

“The detox industry is just a follow-on from that. There’s a lot of money in it and there are lots of people out there in marketing making a lot of money.”

Peter Ayton, a professor of psychology at City University London, agrees.

He says that we’re susceptible to such gimmicks because we live in a world with so much information we’re happy to defer responsibility to others who might understand things better.

“To understand even shampoo you need to have PhD in biochemistry,” he says, “but a lot of people don’t have that. If it seems reasonable and plausible and invokes a familiar concept, detoxing, then we’re happy to go with it.”

Many of our consumer decisions, he adds, are made in ignorance and supposition, which is rarely challenged or informed.

“People assume that the world is carefully regulated and that there are benign institutions guarding them from making any kind of errors. A lot of marketing drip-feeds that idea, surreptitiously.

So if people see somebody with apparently the right credentials, they think they’re listening to a respectable medic and trust their advice.”

Ernst is less forgiving: “Ask trading standards what they’re doing about it. Anyone who says, ‘I have a detox treatment’ is profiting from a false claim and is by definition a crook. And it shouldn’t be left to scientists and charities to go after crooks.”

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Phase II Detoxification

The Science of Detoxification: How Phase I Relates to Health

We are constantly exposed to external, chemical stressors.

These potential toxins, including pollutants, radiation, chemotherapy and smoke inhalation, along with our own internal chemical mediators of prolonged inflammatory response, damage cellular DNA.

This is the necessary precursor for the development of Cancer and is also implicated in chronic illness including Cardiovascular disease, Neurodegeneration, Diabetes, Obesity and Ageing.

Detoxification is crucial in order to remove these potential toxins from the body and optimise long-term health. Our cells have evolved a powerful defence mechanism whereby the enhanced expression of their genes increases the removal of these toxins.

Mounting evidence from studies on population groups and the incidence of disease, so called epidemiology, shows associations between consumption of brassicas such as watercress, with a reduced risk of certain cancers (References 95, 96) including lung, prostate and colorectal cancer (CRC) (References 97, 98)

This review examines current research to understand the process by which Glucosinolate and other antioxidants in brassicas, enhance removal of toxins, specifically through their role in Phase II of this detoxification and therefore have potential to influence the risk of disease.

Detoxification – Phase I and II

The process by which toxins are removed by the body occurs mostly in the liver, but also in the cells lining the digestive tract, kidney and lung and is comprised of two phases of biotransformation:

Phase I involves cytochrome enzymes (P450) which begin the process of chemically transforming fat soluble toxins by oxidisation. This forms an intermediate, Reactive Oxidative Species (ROS), potentially more harmful than the original toxin, which must be further transformed rapidly, by antioxidant action in Phase II.

Phase II enzymes catalyse the addition of compounds onto the reactive intermediate from Phase I, making them more water soluble and therefore more rapidly excreted in bile or urine.

Glucosinolate antioxidants in brassicas, have been found to enhance this enzyme activity by inducing gene transcription of phase II enzymes (Reference 99) and therefore reducing the levels of carcinogens and other toxins, available to damage and mutate DNA.

The Role of Glucosinolate antioxidants

Isothiocyanates (ITCs) are a type of glucosinolate antioxidant in Brassicas. Specifically, studies have shown Phenethylisothiocyanate (PEITC), of which watercress contains the highest levels, to be pivotal in Phase II detoxification.

(Reference 99) Furthermore, in individuals who smoke, and who lack one specific genotype for the Phase II enzyme Glutathione S-Transferase, (GST), research has shown an enhanced effect of PEITC in altering carcinogen metabolism, suggesting the importance of diet in cancer outcomes. (Reference 100)

PEITCs – Mechanism of Action in Phase II Detoxification

PEITCs promote Phase II detoxification by enhancing our ability to produce phase II enzymes. (Reference 101) They do this by altering the expression of gene transcription.

This is known as Epigenetics – heritable changes in gene function, without altering a cell’s DNA sequence, caused by external factors.

(Alterations occur either by increased methylation of the DNA or decreased acetylation of associated histones).

A gene is a small section of DNA within a chromosome located in the nucleus of cells. Genes have ‘promotor regions’ which specific proteins (transcription factors) can bind to, thereby controlling the information which is transcribed from the DNA to its messenger RNA, resulting in the cellular manufacture of proteins required to perform specific functions. 

In phase II detoxification, the binding of transcription factor Nrf2 onto a specific gene promotor region called ARE (Antioxidant Response Element), enables the production of numerous phase II enzymes, including GSTs, by gene transcription.

PEITC has been shown to have a cytoprotective role by activating Nrf2 (Reference 102).

Additionally, in-vivo studies have demonstrated an increase in toxicity of environmental pollutants, medicines, allergens and carcinogens in Nrf2 deficient animals and an associated poorer response to plant chemicals such as PEITC (Reference 99)

It is imperative to note however, that over-activation of Nrf2 activity in existing cancerous cells can lead to resistance to radio- and chemotherapies presumably due to increased drug detoxification, and therefore is associated with a poorer prognosis.

This paradox must be considered when promoting the use of nutrients in health promotion. (Reference 103) Activation of Nrf2 in other chronic diseases related to DNA damage, such as neurodegenerative diseases, diabetes, and cardiovascular disease is however, purely protective.

 (Reference 104)

Watercress, being a rich source of PEITC, clearly has an important potential role in reducing cancer risk and health outcomes of other chronic disease states, due to its ‘naturopathic’ influence on phase II detoxification. In determining future clinical recommendations which  benefit from the effects of food-derived antioxidants such as PEITCs, several factors should be considered:

·         Plant Nutrient Content: Glucosinolates in brassicas vary according to plant health, soil quality and plant microbial content.

·         Influence of the microbiome: Although hydrolysis and therefore activation of Glucosinolates to ITCs by the enzyme myrosinase (in different cells within the same plant) occurs on chewing, giving the characteristic bitter taste, variation exists between individuals on this initial conversion of glucosinolates due to differences in the microbiome, required in addition to myrosinase, for activation. This highlights differences between individuals in their ability to mount effective Phase II detoxification, regardless of the PEITC plant source (Reference 105)

·         Bioavailability of PEITC: 50% of PEITC available in watercress is absorbed.

(Reference 106) ITCs are more ‘available for absorption by the body’ from the raw vegetable form – smoothies for example, than from cooked versions, such as soup.

Additionally, watercress extract has been shown to have more powerful anti-carcinogenic activity than PEITC alone (Reference 107)

·         Bifunctional Mediators: In-vitro studies, i.e.

using cells in a laboratory situation, have shown the function of PEITC to be dependent on its concentration; higher levels being associated with the killing of tumour cells (apoptosis) in prostate adenocarcinomas and CRC (Reference 108).

These same higher levels are also cytotoxic to healthy cells. Caution will therefore be required in determining recommended intake levels for optimal health benefits.

(Reference 102); a variety of smaller amounts of beneficial brassicas possibly being more beneficial by maintaining the balance of nutrients required to optimise phase II detoxification over cytotoxicity. This has been demonstrated in-vivo, with an enhanced effect from an intake combination of watercress, garden cress and broccoli (Reference 109)

·         A role for Vitamin C in Sport Performance: In 2012, Fogarty et al demonstrated an association between watercress intake and reduced post-exercise cell damage (Reference 110).

Further research (Reference 111) has demonstrated reduced biomarkers of cell damage in teenage boys undergoing strenuous activity, after Vitamin C supplementation, presumably associated with increased Phase II detoxification.

However, Powers et al 2011 (Reference 112), reported that excessive intake of antioxidant supplements may impede the body’s own production of antioxidants (which tends to be enhanced in sports performance) A more natural form of antioxidant supplementation, such as Watercress, being rich in Vitamin C and PEITC may therefore be advantageous.