BY RUSSELL BLAYLOCK, MD

We often hear about “detox,” which is short for detoxification. Detoxification can have different meanings for different people. Eating a healthy diet is a loose definition of detoxification.

In fact, this is not only a first line of defense against food-based toxic substances, but it can also stimulate detoxification mechanisms within various tissues and cells, helping to cleanse the body of these harmful compounds.

All cells contain some form of detoxification mechanisms. Key molecules include glutathione—an antioxidant that also binds toxic metals such as lead, mercury, and cadmium—and metallothionein, which helps sequester mercury, cadmium, lead, and arsenic.

Other major detoxification systems include the kidneys and the cells lining the gastrointestinal (GI) tract. The cells lining the GI tract are especially important, as they form a frontline defense against toxic compounds that can enter the body through eating and drinking.

The liver remains the body’s primary detoxification center. It cleanses the circulation of toxic substances that not only enter the body from the GI tract, but also are inhaled into the lungs or absorbed from the skin. Dermal absorption can be a meaningful route for certain substances (e.g., some pesticides, herbicides, cosmetics, and topical medications), though its significance varies by compound and exposure.

After absorption, these chemicals can be widely distributed before hepatic processing. The liver then renders them less toxic and facilitates elimination from the body. Because non-GI exposures do not reach the liver first, some compounds may circulate more widely before detoxification.

To understand how the liver carries out this work, we’ll examine its two-tier detoxification system, known as phase I and phase II detoxification.

Phase I Detoxification

The liver uses a large number of detoxification enzymes classified under the grouping CYP-450 enzymes (sometimes just called P450 enzymes). Chemicals are poisonous because of the specific ways their molecules are structured. To make them less toxic, the liver chemically alters these toxic compounds so they can do no harm. Phase I enzymes serve as the first line of defense, but the system is not perfect.

Keep in mind, modern synthetic chemicals from the pharmaceutical and chemical industries were not present historically; these are new to the liver, which explains why sometimes phase I enzymes, instead of making these new chemicals less toxic, can make them even more toxic or carcinogenic (cancer-causing).

Normally, the liver’s CYP-450 enzymes will attempt detoxification by adding certain chemical groups to the toxic compound to make it less toxic. These include attaching hydroxyl, carboxyl, and amino chemical groups to the toxic molecule. This involves a lot of basic chemistry, so I will spare you all that. Suffice it to say that for about ninety percent of the drugs we are exposed to, this system works very efficiently.

Pharmaceutical drug makers knew that the drugs they were making would be processed by the liver’s chemical factory, so they made allowances for whatever changes the liver would make to their drugs. Most importantly, they calculated how long it would take liver enzymes to neutralize and dispose of each drug. For example, if they gave a drug such as Dilantin—an anti-seizure medication—they had to know how long the liver would let it stay in the body before elimination.

If a medicine is cleared in roughly six hours, it’s prescribed about every six hours to keep blood levels effective. Studies have shown that specific classes of these CYP enzymes are responsible for removing particular drugs. Importantly, certain foods, plant extracts, and herbs can alter the efficiency of these enzymes.

Let us say that an herb designated as R suppressed the enzyme CYP1, which helps remove a particular antibiotic. Using the example above, the antibiotic would be administered every six hours, based on the normal liver’s ability to metabolize the drug. However, if the person were taking herb R, which suppressed the detoxification enzyme CYP1, then the antibiotic would remain in the body longer than the predicted six hours.

Therefore, when the next dose of the antibiotic was administered on schedule, at six hours, a significantly greater amount of the antibiotic would remain from the first dose. Taking the next dose at that time would result in too much of the drug—potentially toxic levels.

The opposite can also happen when a natural supplement stimulates a detoxification enzyme. This time, let us suppose the medication is an anti-seizure drug. Now herb Z stimulates the enzyme that breaks it down. Normally, the anti-seizure medication is administered every eight hours, because that is how long it takes the detoxification enzyme to eliminate the medication.

Suppose the person takes their medication as prescribed. In that case, that is, every eight hours—all will be well, because the blood levels of the anti-seizure medication will be high enough at all times to stop any seizure from happening, until the next dose of the medication.

But if they take herb Z at the same time, the seizure medication level in the blood will run out before the eight hours is up—let’s say it is now mostly gone by four hours. That means that four hours after the first dose, there will not be enough medication in the blood to prevent a seizure. As a result, the patient has a major seizure. Not knowing the effect of herb Z, the patient will be puzzled, since they were taking their medication as prescribed.

Most pharmacists have a list of such drug-supplement interactions, so that such things will not happen.

In nature, we see many procarcinogenic compounds—that is, chemicals that do not cause cancer as is, but must be chemically converted to cause cancer. They are often converted to cancer-causing compounds by the liver’s phase I detoxification system.

This occurs with a variety of pesticides, herbicides, and fungicides, as well as with natural carcinogens such as aflatoxin. The liver is converting these procarcinogens into powerful cancer-causing compounds. For example, the detoxification enzyme CYP1 can convert polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, and polychlorinated biphenyls (PCBs) into fully carcinogenic compounds.

To understand how important the effectiveness of these enzymes can be, when we see low levels of the detoxification enzyme CYP1A2 in a young male, we know that men with this defect have a much higher incidence of developing testicular cancer.

We also see a strong connection between certain detoxification enzyme defects and neurodegenerative diseases. For example, a defect in CYP2D is associated with both a higher incidence of lung cancer and Parkinson’s disease. Certain genetic defects, known as single-nucleotide polymorphisms (SNPs), can cause a single enzyme to function improperly.

Some of the more common genetic defects involving detoxification enzymes include CYP2C and CYP2D. People with these gene defects are called “poor metabolizers” and have great difficulty detoxifying various pharmaceutical drugs, especially drugs that regulate the heart’s rhythm, anti-seizure drugs, and warfarin, a blood thinner. People with this problem must be careful taking these medications—they must follow altered drug schedules. That is, they have to take the medications further apart than normally prescribed.

Another phase I enzyme, CYP2E1, metabolizes anesthetics such as halothane and isoflurane. Such a defect could cause these individuals to encounter difficulty when undergoing general anesthesia.

While phase I detoxification works well most of the time, as we have seen, sometimes it makes errors and actually makes things worse—even deadly. This situation with acetaminophen (Tylenol) is a prime example. Phase I detoxification can cause this drug to do considerable damage to the liver and kidneys, and can even destroy the liver.

In cases where phase I enzymes exacerbate the problem, we may want to inhibit the enzyme responsible. For example, several flavonoids can significantly interfere with the detoxification enzymes that make acetaminophen toxic, namely CYP2E1. One of the more effective naturally occurring compounds is kaempferol, which powerfully prevents damage to the liver via several mechanisms. Curcumin is also a powerful liver protector against many toxic substances.

Fortunately, the liver has a powerful backup system for problems such as this. This backup system is the phase II system, which operates in tandem with phase I, but uses a different set of mechanisms.

Phase II Detoxification

Phase I detoxification reduces toxicity of dangerous compounds circulating in our blood by a process of oxidation—that is, adding compounds that reduce toxicity. Unfortunately, this also makes the toxic chemicals water-insoluble, which could be a big problem because they linger in the liver, where they can cause considerable damage.

To prevent this, phase II detoxification chemically alters these toxic substances to make them water-soluble. Resulting in the toxic compound being eliminated from the body through the kidneys via the urine and through the gastrointestinal tract via the bile.

In chemical language, phase II detoxification is called conjugation—a chemical process where special compounds are added to the toxic molecule to make it water-soluble. These water-soluble chemicals use specific enzymes to perform this process.

These include:

• Glucuronic acid (glucuronyl transferases)

• Sulfate (sulfotransferases)

• Glutathione (glutathione transferases)

• Amino acids (amino acid transferases)

• Acetyl groups (N-acetyl transferases)

• Methyl groups (N- and O-methyltransferases)

When our liver faces a particularly heavy toxic load—for instance, when we have eaten a lot of junk food or foods contaminated with high concentrations of agrichemicals—our liver increases the concentration of these phase II detoxification enzymes to handle the new load.

The same is true with internal toxic compounds, such as when we are sick, exercise strenuously, or are injured. In all such cases, the blood becomes contaminated with significantly more dead cells than usual, along with harmful metabolic products.

Keep in mind that our hormones are also constantly metabolized by the liver, and when the liver is functioning abnormally, our hormones are also impacted. Under specific circumstances, this can raise our risk of certain hormone-dependent cancers, such as prostate and breast cancers. These detoxification enzymes also change during pregnancy, old age, and living in environments with high levels of pollution.

Many toxic substances can even damage some of the detoxification enzymes, thus impairing the efficient detoxification of other dangerous compounds.

Recently, researchers discovered that an impairment of specific types of glucuronyl transferase enzymes can greatly increase a person’s risk of colon cancer. This discovery highlights the crucial role of these detoxification enzymes.

Similarly, a number of studies have shown that exposure to pesticides, herbicides, and certain fungicides can greatly increase a person’s risk of developing Parkinson’s disease, especially if they have a defect in one of these enzymes. This effect was demonstrated in a medical journal which described the alarming experience of a woman who decided to clear her house of insects by spraying everything in sight with a household insecticide. Soon afterward, she developed a very rapid onset of advanced Parkinson’s disease.

She was admitted to a local hospital, and the neurologist confirmed that she was indeed suffering from advanced Parkinson’s, which was unusual because advanced cases can take decades to develop. Over a short period, she made a complete recovery and returned home. Her family thoroughly cleaned her house before she returned. Immediately upon reentering her home, all her Parkinson’s symptoms returned.

She was hospitalized again, and once again she recovered. Convinced the house was beyond any hope of decontamination, she and her husband moved to a new home free of contamination. She did well until her family brought one of her blouses from the old house. Once she put it on, all her symptoms returned.

Most notably, this never happened to her husband, even though he lived in the same house, and none of her relatives experienced any problems when visiting the home. It was concluded that the poor lady had a defect in one or more detoxification enzymes needed to neutralize the insecticide, and, as a result, even extremely small amounts of the bug spray caused her to develop advanced Parkinson’s disease-like symptoms.

One of the strongest links to Parkinson’s disease is chronic exposure to pesticides, herbicides, and fungicides. The reason appears to be that they can overwhelm the liver’s ability to detoxify these harmful chemicals. People born with certain genetic defects such as SNPs, affecting specific detoxification enzymes, are much more susceptible to such chemically induced neurodegenerative diseases.

As we age, the liver’s ability to detoxify these poisons can become impaired as well. This puts us at high risk of harm from exposure not only to environmental poisons but also to toxic substances.

Sulfotransferase enzymes are another mechanism used in the phase II system to make toxic compounds water-soluble. Here, sulfur groups are chemically bonded to these toxic substances. This type of detoxification is crucial for metabolizing hormones, including thyroid hormone, estrogens, and androgens. The sulfur-containing amino acids, particularly taurine, are crucial for supporting this type of detoxification. Garlic and onions are also important sources of these sulfur compounds.

Another part of phase II detoxification utilizes an enzyme called glutathione-S-transferase. Regularly taking acetaminophen can drastically lower glutathione levels, which depletes this important detoxification system. The transfer of acetyl chemical groups to toxic compounds is important for detoxifying certain drugs containing hydrazines or aromatic amines, such as isoniazid, hydralazine, and sulfonamides. Defects in this detoxification enzyme can result in a high incidence of drug reactions and liver damage.

Finally, several natural compounds contribute a methyl group for the detoxification of potentially toxic compounds and for metabolizing estrogens. The amino acid methionine, vitamins B12, B6, folate, and betaine are important for supporting this form of detoxification. You may recall the craze some years ago when people were taking a product called SAMe for depression. SAMe (S-adenosyl-L-methionine) is also a methyl donor used in the detoxification process.

Food, Plant Extracts, and Other Nutritional Supplements Affecting Detoxification

Several vegetables and plant extracts can alter the various enzymes used by the liver for detoxification. When dealing with certain plant extracts or components, it is important to appreciate that the dose is essential. For some compounds, such as curcumin—an extract from the spice turmeric—a low dose stimulates the phase I enzyme CYP1A1, whereas a higher dose suppresses it, which may be good or bad, depending on the situation.

To prevent a procarcinogen from being converted into a fully active carcinogen, one may want to suppress certain detoxification enzymes. Under such circumstances, a higher dose of curcumin would be advantageous. Celery also inhibits this enzyme.

Under most circumstances, this is beneficial because it prevents phase I enzymes from producing cancer-causing compounds. Yet, suppressing a detoxification enzyme could be harmful if a particular pharmaceutical drug requires this enzyme for its metabolism. Even then, it is a matter of reducing the dose of the medication or changing the scheduling for how often to take the drug.

Sometimes it is all a matter of the total effect of a food or plant extract. For example, cruciferous vegetables (such as kale, Brussels sprouts, and broccoli) and resveratrol (and resveratrol-containing plants) can induce this same enzyme; however, these plants contain a number of anti-cancer compounds that easily override any effect of stimulating this detoxification enzyme.

In many studies examining the effects of plants or plant extracts, researchers used very high doses—far exceeding what a person would normally consume. Yet we should not ignore these interactions, especially when dealing with pharmaceutical drugs.

Other commonly consumed food items that can affect phase I detoxification include rooibos tea, garlic, fish oil, green tea, black tea, and quercetin. These compounds all affect one of the more clinically important detoxification enzymes, the CYP3A group. This group of enzymes is used to detoxify caffeine, testosterone, progesterone, and the carcinogen aflatoxin B1. It is also responsible for detoxifying over fifty commonly used pharmaceutical drugs.

Grapefruit juice is the best-known inhibitor of this enzyme. Drinking grapefruit juice can significantly prolong caffeine’s shelf-life in the body and, if coffee is consumed too late at night, can result in severe insomnia. On the other hand, curcumin stimulates this enzyme, meaning it will reduce the time caffeine stays in your system.

Plant effects are even more complicated. Take, for example, cruciferous vegetables, such as broccoli. These plants contain a substance (sulforaphane) that inhibits the CYP3A enzymes but also contains indole-3-carbinol, which increases the enzyme’s activity. In essence, one plant compound counteracts the effects of another.

Many plant flavonoids improve phase II function. Cruciferous vegetables, for example, can enhance UDP-glucuronosyltransferase activity, which is a critical phase II detoxification enzyme. Other foods that stimulate these beneficial enzymes include dandelion extract, rooibos and honeybush teas; pumpkin; carrots; squash; sweet potatoes; collards; red pepper; apples; onions; kale; cherries; red wine; extra-virgin olive oil; beans; Brussels sprouts; broccoli; grapefruit; tomatoes; rosemary; ellagic acid; ferulic acid; curcumin; and astaxanthin.

Magnesium-rich foods are also crucial for liver detoxification. These include halibut, almonds, cashews, spinach, oatmeal, peanuts, and wheat bran, in order of magnesium content. Keep in mind that the most important of our two systems for detoxification protection is the phase II system. This is the one that removes toxic substances from your body.

A wide range of natural products has been demonstrated to enhance glutathione levels in the liver and other cells. These include curcumin, silymarin, folic acid, N-acetyl-L-cysteine (NAC), duck, egg yolks, cheese, red peppers, garlic, onions, and R-lipoic acid, among others. Glutathione itself is a powerful detoxification compound that can be taken in liposomal supplement form found in local health food stores.

Additionally, several foods increase the sulfur content needed for this type of detoxification. These include scallops, lobster, crab, peanuts, shrimp, veal, Brazil nuts, haddock, sardines, and eggs, in decreasing order.

While most attention has been paid to how foods either stimulate or inhibit these detoxification enzymes, more recent research has found that several natural products, rather than either stimulating or suppressing detoxification enzymes, modulate them.

This means they stimulate the enzymes if they are deficient and suppress them if they are overactive—the best of both worlds. Pomegranate, curcumin, cruciferous vegetables, green tea, and artichoke hearts seem to possess this modulation property, which is very valuable.

We should also keep in mind that many natural compounds are highly protective of the liver through various mechanisms beyond their effect on detoxification enzymes.

For example, many are powerful antioxidants and anti-inf lammatory agents, suppress cancer development, engage in antimicrobial activity (killing bacteria, viruses, and fungi), and increase the generation of factors that stimulate liver regeneration, such as sirtuins and Bcl-2. Curcumin, quercetin, silymarin, and several of these carotenoids have these properties.

The liver’s remarkable detoxification system represents one of the body’s most sophisticated defense mechanisms—yet it was never designed to handle the chemical onslaught of modern life. Understanding how phase I and phase II pathways work and supporting them with targeted nutrition and lifestyle choices empowers us to work with our biology rather than against it.

From the glutathione-boosting power of curcumin to the phase II support of cruciferous vegetables, nature provides the tools we need to enhance our detoxification capacity.

The key is consistent, daily support through whole foods, strategic supplementation, and mindful reduction of toxic exposures. When we give the liver the resources it needs to function optimally, we’re not just supporting one organ—we’re investing in whole-body health and resilience for years to come.

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Russell Blaylock, MD, is a nationally recognized, award-winning health practitioner and medical doctor, board-certified in both neurosurgery and clinical nutrition. He is a prolific contributor to peer-reviewed medical journals and the author of numerous books, including Dr. Blaylock’s Prescriptions for Natural Health. He also writes a popular monthly newsletter, The Blaylock Wellness Report, published by Newsmax.

Well Being Journal adapted the above excerpt from The Liver Cure by Russell Blaylock, MD. Copyright © 2022 by Humanix Books. Reprinted with permission from Humanix Books.