The Liver & Detoxification (Part 2)

By Graeme Bradshaw


  • Lethargy / fatigue (especially upon waking)
  • Headaches or migraines with nausea
  • Yellowish tine to white of the eyes
  • Bruising very easily (capillary fragility)
  • Muscle ache, stiffness of joints, rheumatism worse in morning
  • White or yellow coated tongue, bad breath
  • Unclear skin, like acne or boils & some rashes
  • Intolerance to alcohol & chemical sensitivity (e.g. to perfumes), and other allergies developing as an adult
  • Fluid retention and/or congested lymph glands or sinuses
  • Dark circles under the eyes or puffiness around eyes
  • Excessive body fat and high LDL cholesterol, fatty liver and gall stones
  • Digestive complaints, such as bloating and fullness
  • Constipation - less than seven bowel motions a week
  • Poor concentration and memory, hyperactivity, Attention Deficit Disorder
  • Poor physical balance and fine motor skills, hand tremors (damage to cerebellum)
  • Tendency to negative thinking/feeling- moody – as in a hangover worse on waking


The liver is an essential organ that is responsible for several major metabolic and digestive functions of the body. One of its most important functions is to detoxify the body by neutralizing and eliminating the extra toxins that our bodies are exposed to on a daily basis. When optimum nutrition is provided, the liver operates efficiently. A great many people, however, do not eat the right kinds of foods or sufficient nutrients that provide the liver with everything it needs for the detoxifying process. If nutrition is compromised through poor dietary and lifestyle habits, the detoxification process will be impaired and other organ functions will suffer as the body retains the toxins it cannot eliminate. Also, if the bowel is constipated (less than a bowel motion daily), then many of the toxins eliminated from the liver through the bile just get reabsorbed in the small intestine, and return to the liver. If the gut flora is imbalanced, then the toxic bacteria or yeasts in the intestines create even more toxic chemicals – and the vicious cycle of toxic overload is then experienced.

The rate at which the liver can eliminate toxins can determine an individual's susceptibility to toxic overload, which in turn can lead to symptoms of ill-health. When the liver becomes so overloaded with harmful toxins that the liver's enzymes can no longer cope, the toxins build up and this then manifests itself in a specific disease state. Without the intervention of correct nutrition, this state can become a vicious circle of chronic toxic overload, as detailed in the diagram below.

Vicious circle of chronic toxic overload


Many inflammatory conditions such as arthritis, cardiovascular problems, headaches, chronic fatigue, and premature ageing can all be caused and aggravated by a buildup of toxins that the liver is unable to cope with.

Read on to learn about the liver's detoxification process, and how proper nutrition and supplements can enhance this vital function.


Two phases of liver detoxification


The liver uses a two-step enzymatic process to neutralize unwanted chemical compounds. These compounds include toxins such as drugs, pesticides, and toxins from the gut, as well as normal body chemicals such as hormones and inflammatory chemicals (e.g., histamine) that become toxic if allowed to accumulate in the body. Some chemicals, if left to build up, can cause substantial damage, including the initiation of carcinogenic processes.

The Phase I Detoxification Pathway

Phase I detoxification of most chemical toxins involves a group of enzymes which, collectively, have been named cytochrome P-450. Some 50 to 100 enzymes make up the cytochrome P-450 system. Each enzyme is suited to detoxify specific types of chemicals, but there is considerable overlap in activity among the enzymes. These enzymes reside on the membranes of liver cells called hepatocytes. Human liver cells possess the genetic code for many types of P-450 enzymes, so when the body is exposed to different toxins, the liver will be induced to synthesize the specific enzymes required to neutralize them. This mechanism protects the body from the damaging effects of a wide variety of toxic chemicals.

This pathway neutralizes a toxin by simply converting it into something that is chemically in smaller pieces that will be handed over to Phase II, or, alternatively, makes it water-soluble, which allows its excretion by the kidneys or through sweating. This pathway uses various chemical reactions such as oxidation, reduction, and hydrolysis.

A significant side effect of Phase I detoxification is the production of free radicals as the toxins are transformed. For each molecule of toxin metabolized by Phase I, one free radical molecule is generated. Without adequate free radical defenses, every time the liver neutralizes a toxin, it is damaged by the free radicals produced. Antioxidants, such as reduced glutathione, vitamins C and E, carotenoids, flavenoids and selenium reduce the damage caused by these free radicals. If antioxidants are deficient and toxin exposure is high, toxic chemicals become far more dangerous. The activity level of the various cytochrome P-450 enzymes varies significantly from one individual to another. An individual's genetics, level of exposure to chemical toxins, and his or her nutritional status all affect the level of enzyme activity. Since the activity of cytochrome P-450 varies so widely, an individual's risk of disease also varies widely. For example, the variability of a person's ability to detoxify the carcinogens found in cigarette smoke helps to explain why some people can smoke with only modest damage to their lungs, while others develop lung cancer after only a relatively short time of smoking.

People with underactive Phase I detoxification will experience intolerance to perfumes and other environmental chemicals and are at an increased risk for liver disease. In addition, these people will experience caffeine intolerance, while those with an overactive system will be relatively unaffected by caffeine. By the way cardamom spice raises the phase I enzyme that detoxifies caffeine, so adding some cardamom powder to teas or coffees is beneficial, especially if you are sensitive to caffeine.

One way of objectively determining a person's Phase I activity level is to measure how efficiently his or her body detoxifies caffeine. This test has discovered that apparently healthy adults can have a five-fold difference in detoxification rates, and that this variability applies to most other toxins as well. This is mostly genetically governed. People with a diminished capacity to detoxify are at greater risk of several toxin-induced illnesses.

Excessive amounts of toxic chemicals such as pesticides can disrupt the P-450 enzyme system by causing over-activity, or what is called "induction" of this pathway. This results in high levels of damaging free radicals being produced as explained above. Substances that may cause induction are caffeine, alcohol, dioxin, saturated fats, organophosphate pesticides, paint fumes, sulfonamides, exhaust fumes, heavy metals and barbiturates.

The problem with these particular toxins is that too much activity may overload the body's stores of antioxidants and the Phase II system, which in turn may lead to increased inflammation, liver damage and/or cancer rates. The metabolites produced during Phase I are often potentially more harmful than their original toxic compounds, therefore it is important that they are not allowed to build up. This is where Phase II detoxification comes in, if there are sufficient levels of Phase II enzymes to complete the enzymatic bio-transformation.

The Phase II Detoxification Pathway

Phase II is the second stage in processing toxic compounds for elimination. This phase involves the addition of chemical groups (e.g., glutathione, glycine or taurine) to the toxic compound that make the it less toxic to body tissues and easier to excrete. During Phase II, the liver adds small chemical pieces onto the toxin in a process called conjugation – effectively wrapping it up safely. These conjugation reactions include sulphation, glucuronidation, and glutathione conjugation, which are key processes to healthy detoxification. Methylation, acetylation, and amino acid conjugation are the reactions used to prepare toxins for release into bile.

The conjugation reaction (wrapping effect) neutralizes toxins and the intermediate compounds left over from Phase I. For efficient Phase II detoxification and production of bile, the liver cells require sulphur-containing amino acids such as taurine and cysteine, and several other nutrients as explained in more detail below. The right foods will provide these, so read on to find out how to support detoxification with foods, herbs and supplements.

The Main Detoxification Enzyme: Glutathione

Glutathione also plays a fundamental role in numerous metabolic and biochemical reactions. As the most powerful liver and brain detoxifier and protector, glutathione has multiple functions. First, as the major antioxidant produced by the cells, it participates directly in the neutralization of free radicals. It also maintains antioxidants such as vitamins C and E in forms that can be used by the body. Through direct conjugation, it detoxifies many foreign chemical compounds and carcinogens, both organic and inorganic, and also heavy metals such as mercury, lead, and arsenic. It is also critical for removing air pollutants such as volatile organic chemicals, and also many pesticides. Every system in the body can be affected by the state of the glutathione system. The immune system, the nervous system, the gastrointestinal system, and the lungs are especially affected.

The lack of this enzyme reduces the body's ability to detoxify alcohol. Many Chinese and other East Asians have inherited an inability to produce sufficient quantities of the enzyme needed to detoxify alcohol. This condition can cause flushing skin reactions once alcohol is taken. Anyone with low alcohol tolerance is advised to take a milk thistle supplement to support the production of liver enzymes and help proper detoxification, even when they are not taking alcohol as this is the simplest way to support the low glutathione levels.

The Glucuronidation Pathway

The glucuronidation process removes hormones such as testosterone, oestrogen, and steroids; fatty acid derivatives, bilirubin, and bile acids. Many commonly used substances, such as aspirin, menthol, synthetic vanilla, acetaminophen, morphine, diazepam, digitalis, and benzoates are detoxified through the glucuronidation pathway.

About 5 percent of the population has Gilbert's Syndrome, an inherited impairment of the glucuronidation pathway. Gilbert's syndrome is a benign condition characterized by jaundice and elevated levels of bilirubin. A patient with Gilbert's syndrome typically complains of loss of appetite, malaise, muscle pains, nausea, headaches or migraines and fatigue, hormonal imbalance and may have a slightly yellowish tinge to the eyes. All of these symptoms are typical indications of liver dysfunction. Limonine (derived from teas of citrus peel) or dill seeds help relieve symptoms, as does methionine, administered as SAMe (obtained from a nutritional supplement).


Liver dextoxification pathways

Source: Healthscope Practitioner Manual

The entire liver detoxification process requires certain nutrients in order to function properly. The Phase I cytochrome P-450 pathway requires several cofactors and enzymes, such as riboflavin (B2), niacin (B3), and magnesium. To neutralize the free radicals that are produced during Phase I, the body requires antioxidants, such as carotenoids, flavenoids (from yellow and red/purple fruits respectively) and vitamins C and E, and selenium (the latter two mostly obtained from wholegrain cereals and nuts or seeds).

The nutrient requirements of the various Phase II pathways, and their sources, are as follows:

Glutathione conjugation: glutathione, vitamin B6, cysteine (NAC is the best source), glutamic acid, and glycine.

Amino acid conjugation: mainly glycine, but also glutamine, ornithine, taurine, arginine.

Methylation: mainly S-adenosyl-methionine (SAMe), which is normally made from methionine (in most protein foods) and homocysteine, provided there are sufficient B vitamins. Also requires the lipotropic (fat mobilizing) nutrients choline, methionine, betaine (from beetroot), folate (from green vegetables), vitamin B12 (from meats or dairy), and B6 (from whole grains and nuts).

Sulphation: cysteine, taurine, inositol, choline, methionine, and molybdenum. These nutrients are mostly provided by eggs and cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower, and raw garlic, onions, leeks, and shallots.

Acetylation: acetyl-CoA, derived from normal metabolism.

Glucuronidation: glucuronic acid, available in gum Arabic, agar agar gel and apples. The process is stimulated by dill oil, limonene, and caraway seeds.

Supporting Glutathione Production and Glucuronidation

The most important antioxidant for neutralizing the free radicals produced in Phase I is glutathione. In addition, glutathione is required for one of the key Phase II detoxification processes. When high levels of toxin exposure produce so many free radicals from Phase I detoxification that glutathione is depleted, the Phase II processes that depend upon glutathione stop working. In fact, the ratio of the main active form of glutathione (reduced glutathione) to depleted glutathione within the cells (oxidized glutathione) is often used as a measure of cellular toxicity. Once glutathione is depleted or oxidized, immunity is poorly regulated, as is the nitric oxide cycle governing blood pressure. Also carcinogens such as pesticides and heavy metals build up when glutathione is depleted. In the section following you can discover what foods and supplements can support the crucial glutathione level.

Glutathione levels and the glucuronidation process are influenced by diet, as described below:

  • Milk thistle herb stimulates both glucuronidation and glutathione activity, and is the most commonly taken supplement for the liver.
  • Flavonoids from red grapes and blueberries help regenerate depleted glutathione levels. Grape seed extract is an excellent supplement.
  • Selenium is crucial for recycling glutathione and is regarded as an anticancer nutrient as a result. It is highest in brazil nuts, but also found in wholegrain products – especially those organically grown
  • Whey powder is a good source of cysteine, the critical amino acid needed for glutathione production, and supplies most other sulphur containing amino acids such as taurine for the sulphation process.
  • Green tea encourages glucuronidation mechanism, as does Limonene oil, found in citrus peel, dill weed oil, and caraway oil.
  • Whey powder, eggs and cruciferous vegetables (e.g., broccoli, cabbage, brussels sprouts, cauliflower), and raw garlic, onions, leeks and shallots are all good sources of the natural sulphur compounds that enhance the Phase II detoxification reaction called sulphation. Thus, these foods can be considered to have a cleansing effect.

Among foods, the Brassica or cabbage family (cabbage, broccoli, and brussels sprouts) contains chemical compounds that stimulate both Phase I and Phase II detoxification enzymes. One such compound is indole-3-carbinol, which is also a powerful anti-cancer chemical. It is a very active stimulant of detoxifying enzymes in the gut as well as the liver. It potently neutralizes the carcinogenic activity of estrogens, and women who take brassicas regularly have significantly less breast cancer. The net result is significant protection against several toxins, especially estrogenic carcinogens. This helps explain why consuming these vegetables protects against several types of cancer, including bowel cancer.

Oranges and tangerines (but not grapefruits), as well as the seeds of caraway and dill contain limonene, a phytochemical that has been found to prevent and even treat cancer in animal models. Limonene's protective effects are probably due to the fact that it is a strong inducer of both Phase I and Phase II detoxification enzymes and also helps to neutralize carcinogens.

Curcumin, the compound that gives turmeric its yellow color, is interesting because it inhibits Phase I while stimulating Phase II. It is particularly effective in regenerating glutathione after it has been oxidized. This effect can be very useful in preventing certain types of cancer. Curcumin has been found to inhibit carcinogens (such as benzopyrene, found in charcoal-grilled meat) from inducing cancer in several animal models. It appears that curcumin exerts its anti-carcinogenic activity by lowering the activation of carcinogens through its anti-oxidant property while simultaneously increasing detoxification by improving the active form of glutathione (glutathione reductase). Curcumin has also been shown to directly inhibit the growth of cancer cells, particularly lung and bowel cancer cells.

As most of the cancer-inducing chemicals in cigarette smoke are only carcinogenic during the period between activation by Phase I and final detoxification by Phase II, curcumin in can possibly help reduce the cancer-causing effects of tobacco. Those exposed to smoke, aromatic hydrocarbons, and other environmental carcinogens will probably benefit from the frequent use of turmeric. (Note that curries usually have too little turmeric content to be effective).


Inhibitors of Phase I Detoxification

Many substances inhibit cytochrome P-450 activity. This situation can cause substantial problems, as it makes toxins potentially more damaging because they remain in the body longer before detoxification. For example, grapefruit juice decreases the rate of elimination of drugs from the blood and has been found to substantially alter their clinical activity and toxicity. Eight ounces of grapefruit juice contains enough naringenin to decrease cytochrome P-450 activity by a remarkable 30 percent. This process is employed in allopathic medicine for transplant patients, as it delays detoxification of anti-rejection drugs such as cyclosporin and allows these drugs to stay in the body longer. Avoid grapefruit juice, wheras lemon supports detoxification. A good way to start the day is slices of lemon in hot water.

Substances known to inhibit Phase I detoxification include drugs such as benzodiazepines, antihistamines, cimetidine and other drugs that block the secretion of stomach acids, ketoconazole, and sulfaphenazole. In foods, naringenin from grapefruit juice, curcumin from turmeric, capsaicin from chili peppers, eugenol from clove oil, and quercetin from onions all diminish Phase I activity. Some botanicals are also known to have the same effect, such as calendula, kava kava and possibly St John's wort, as do toxins from inappropriate bacteria in the intestine.

The activity of Phase I detoxification enzymes decreases with advancing age and deficiencies of Vitamin B2, B3, copper, magnesium, and zinc - the latter two being deficient in most Western diets. Ageing also decreases blood flow through the liver, further aggravating the problem. Lack of physical activity necessary for good circulation, combined with poor nutrition commonly seen in the elderly, add up to a significant impairment of detoxification capacity in ageing individuals. This helps to explain why toxic reactions to drugs are seen so often in the elderly.

Recent research shows that the cytochrome P-450 enzyme systems are also found in other parts of the body, especially the brain cells. Inadequate antioxidants and nutrients in the brain result in an increased rate of neuron damage, such as the type seen in Alzheimer's and Parkinson's disease patients. Turmeric's curcumin appears to reduce this problem.

Inhibitors of Phase II Detoxification

In general, increased exposure to toxins as well as a poor dietary supply of glutathione can soon lead to glutathione depletion and increased damage from the highly reactive intermediate compounds. Oral supplementation with reduced glutathione, high doses of vitamin C or supplements of N-acetylcysteine or Milk Thistle can be key to helping increase glutathione levels.

In addition, glutathione conjugation is inhibited by excessive alcohol consumption, paracetamol, acetaminophen, antibiotics, exposure to heavy metals and pesticides, selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency, lack of flavonoids and other antioxidants from fruits and vegetables, and a lack of vitamin E from whole grains and nuts.

Amino acid conjugation is inhibited by a low protein diet, while the methylation process is inhibited by a folic acid or vitamin B12 deficiency caused by a lack of green vegetables (folate) or some animal product (B12).

The sulphation process is inhibited by non-steroidal anti-inflammatory drugs, tartrazine (yellow food dye), steroids, and a molybdenum deficiency.

Acetylation is inhibited by a deficiency of vitamin B2, B5, or C.

The glucuronidation process is inhibited by drugs such as oral contraceptives, aspirin, probenecid, diazepam, some pesticides and phenolic compounds in air pollution and overuse of paracetamol. About 33% of all drugs are detoxified by this pathway. The blockage or slowdown of this system is associated with gallstones.


The Need for High Metabolic Energy

High levels of toxins tire the system because detoxification requires a lot of metabolic energy. It takes a lot of energy for the liver to synthesize some of the small conjugating molecules, particularly the essential glutathione. Thus, low cellular energy production (mitochondrial dysfunction), such as is found in people suffering from chronic fatigue syndrome, or a deficiency of magnesium, vitamin B, or coenzyme-Q10, or a sedentary lifestyle can cause Phase II detoxification to slow down, allowing the build-up of toxic intermediates. Alcohol and high blood sugar levels related to diabetes commonly induce magnesium and B complex deficiency, which can also slow metabolic energy production. Lack of antioxidants tends to do this as well, as it lowers both detoxification activity and overall vitality.

Are You a Pathological Detoxifier?

In some people, the two detoxification pathways are out of balance. If Phase I is more active than Phase II, a build-up of reactive intermediate metabolites can occur, which in turn can lead to tissue damage and disease. These people are referred to as pathological detoxifiers. Pathological detoxifiers can be identified as those individuals who are highly sensitive to fumes (e.g., paints and perfumes), react adversely to various pharmaceutical drugs, and may have a reaction to drinking caffeine. A liver detoxification test can pinpoint exactly how efficiently your liver is carrying out the detoxification process and determine if your symptoms arise from a phase imbalance. Liver function can be evaluated with the Functional Liver Detoxification profile test available at IMI. You can determine such things as the phase I: phase II ratio and levels of each of the main types of detoxification processes discussed above.

Correcting pathological detoxification or a lack of Phase II enzymes may reduce risks of cancer from both pollutants and hormones. Pathological detoxifiers may also find it useful to include grapefruit juice, foods from the cabbage family, and curcumin-rich turmeric in their diets, as well as stopping coffee.

Funtion liver detoxification profile

Source: Healthscope Practitioner Manual

General Dietary Guidelines for Optimum Detoxification

The diet should include plenty of organic, unrefined, unprocessed foods, as fresh as possible and in their natural state. Fresh vegetables, fruits, whole grains and unrefined wholegrain foods such as brown rice, rye bread, wholemeal pasta such as soba or spelt pasta, and legumes are great sources of relevant nutrients and should make up the majority of the diet. A minimum of one daily serving of brassica vegetables and at least two servings of fresh fruit should be included in the daily diet. Use the spices turmeric, cumin, caraway, and dill seeds often.

Red meats, animal fats, sugars, and refined foods should be limited, as should caffeine and other stimulants, and alcohol. Protein sources can be obtained from eggs, fish, lentils, soya, and bean dishes (e.g., dahl and hummus), as well as nuts, seeds, and free range chicken.

Drink plenty of bottled water or diluted juice -- at least two litres per day.

In summary, it can be said that an efficient liver detoxification system is essential for health and having plenty of vitality. In order to support this process, it is essential that many key nutrients are included in the diet.

Many people choose to follow an enhanced detoxification programme, which may take many forms. It should be noted, however, that any such programme should be supervised by a qualified naturopath because when toxins are released too quickly, this can be extremely uncomfortable and may cause headaches, fatigue, diarrhoea, irritability, and lightheadedness. We at IMI use supportive supplements to conjugate or wrap up these toxins as they are being released, minimizing the physical symptoms while detoxifying. It is a poorly designed detoxification programme if you have headaches or much physical discomfort while detoxifying.

Removal of toxins gives many positive health benefits, such as increased energy, clear skin, vitality, and a general feeling of well-being.

Supplements to Support Detoxification

At IMI, several supplements are available to help support liver detoxification. Innate's Antioxidants or Innate's Multivitamin (Men's Multi or Women's Multi) are whole-food sources of antioxidants.

Our liver detoxification combination for everyday use, DeTox Formula, contains milk thistle, curcumin, and other important Phase II support nutrients such as N-Acetyl-Cysteine, glycine, grape seed extract, green tea.

An alternate product called Fast and Be Clear can be used as a meal replacement. This is used in our Clinical Detox: 10 Days For Busy People programme, as it has all of these nutrients in a convenient meal-replacement powder form that can be mixed with juice. The Clinical Detox: 10 Days For Busy People programme also helps promote weight loss.