A Physician’s Primer to Liver “Detoxification:” Cleaning Out the System


The body expends a tremendous effort to maintain and grow. Chemical protection from the environment is represents the body’s greatest expenditure of energy & resources. While the skin may be the largest organ of ‘detoxification,’ followed by the lungs, the liver represents the best recognized organ system involved in the detoxification of digestive, environmental and metabolic poisons.

The liver demonstrates outstanding regenerative abilities. Routinely rebounding from trauma and chemical insult, the liver is a remarkable organ. Like other organs, it requires proper care and maintenance for proper health and long service life.

In many medical cultures, including allopathic, traditional, non-traditional, oriental and alternative, attention is paid to periodic ‘detoxification’ providing a healthy break for organs, such as for the liver, kidney, lung, bladder and gallbladder.

It has been said that ‘Scientific’ data is difficult or to obtain in support of the observations of  the many thousands of persons over many centuries, but it is very clear that there is something to the claims that liver detoxification in particular makes people feel better. The complexities of liver metabolism make it very difficult to evaluate the entire system with regards to ‘detoxification,’ but some things are easily demonstrable: Many of the traditionally used herbals and many of the available chemical antioxidants function to purge the biliary and pancreatic tracts through well delineated and well understood chemical means. For example, it is well known how a commonly used detoxifier, N-Acetyl Cysteine (NAC) influences hepatic metabolism resulting in normalization of function, reducing elevated liver function enzymes, and increasing biliary/pancreatic flow. Glutathione, L-Theanine, silymarin and aloe are among the most commonly used agents and some of the safest medications available.

Without getting into the basics of what is known as ‘phase 1” and ‘phase 2’ detoxification, which is the paradigm that outlines the manner in which the liver, lung, kidneys, skin ‘detoxify’ substances, there is a lot of good to be said for engaging in the periodic practice of ‘liver detoxification.

Let’s Start with the Basics.

What are the functions of the liver? 

  1. It is responsible for the production of bile which is stored in the gallbladder and released when required for the digestion of fats.
  2. The liver stores glucose in the form of glycogen which is converted back to glucose again when needed for energy.
  3. It also plays an important role in the metabolism of protein and fats. It stores the vitamins A, D, K, B12 and Folate and synthesizes blood clotting factors.
  4. Another important role is as a detoxifier, breaking down or transforming substances like ammonia, metabolic waste, drugs, alcohol and chemicals, so that they can be excreted. These may also be referred to as “xenobiotic” chemicals.

If we examine the liver under a microscope, we will see rows of liver cells separated by spaces which act like a filter or sieve, through which the blood stream flows. The liver filter is designed to remove toxic matter such as dead cells, microorganisms, chemicals, drugs and particulate debris from the blood stream. The liver filter is called the sinusoidal system, and contains specialized ‘Kupffer Cells’ which metabolize, or breakdown toxic matter.

The ‘poor man’s liver detox-

The gall bladder functions to store bile between meals. The gall bladder contracts when stimulated to push bile salts into the small bowel, thereby facilitating digestion. Bile is a clear, yellow liquid, when healthy. If the bile is allowed to stagnate, or if the gallbladder is allowed to distend or get infected, the bile thickens, stones form, and mucous backs up. Sometimes, this leads to medical conditions that result in the need to surgically remove the gallbladder.

As it were, prevention is probably the best bet, when dealing with the liver/gallbladder system. A little bit of care, and a little bit of prevention goes a long way.

To keep the gallbladder from distending and to keep the bile from ‘going stale,’ the daily administration of silymarin, taken with each meal, will keep things moving along. Essentially, the gallbladder should be emptied in the same way that the bladder and colon must be purged. Silymarin (milk thistle) stimulates the gall bladder to ‘dump, ‘ very much in the same way the colon does.

Both the colon and gallbladder should empty with each meal. With infection, the bile will thicken, stones will form and chronic inflammation will result. After removal of the gallbladder, the bile will thicken. Thinning of the bile, that is, decreasing biliary viscosity is one focus of ‘liver detoxification.’

The liver is the cleanser and filter of the blood stream and is of vital importance. It is the largest organ in the body and has an enormous amount of blood flowing through it every minute of our lives. It is between 21 – 22.5 cm in its greatest diameter, 15 – 17.5cm in its greatest height and 10 – 12.5 cm in its depth, weighing around 1200 – 1600 gm.

We have been attacking the symptoms of weight excess with fad diets, high impact aerobics, and stomach stapling and toxic drugs, such as appetite suppressants, laxatives and diuretics. We have failed to consider the underlying cause of LIVER DYSFUNCTION and indeed we have virtually ignored the hardest-working organ in the body, with dire consequences.

There are many chemicals (e.g., trace metals, industrial chemicals, and mycotoxins) that may be inadvertently present in animal tissues yet have no established safe concentrations. This of course does not mean that these substances are not harmful.

It is a fact of life that pesticides, herbicides and hormones are used in food production. Although the regulatory levels set by authorities provide some control over residues – it is not the ‘be all and end all’. The liver is again highlighted as vital, as it is the organ that metabolizes these substances and excretes them from the body.

The liver is the gateway to the body and in this chemical age its detoxification systems are easily overloaded. Thousands of chemicals are added to food and over 700 have been identified in drinking water. Plants are sprayed with toxic chemicals, animals are injected with potent hormones and antibiotics and a significant amount of our food is genetically engineered, processed, refined, frozen and cooked. All this can lead to destruction of delicate vitamins and minerals, which are needed for the detoxification pathways in the liver. The liver must try to cope with every toxic chemical in our environment, as well as damaged fats that are present in processed and fried foods.

Phase One – Detoxification Pathway

Human liver cells possess the genetic code for many isoenzymes of P-450 whose synthesis can be induced upon exposure to specific chemicals. This provides a mechanism of protection from a wide variety of toxic chemicals.

To put it simply, this pathway converts a toxic chemical into a less harmful chemical. This is achieved by various chemical reactions (such as oxidation, reduction and hydrolysis), and during this process free radicals are produced which, if excessive, can damage the liver cells. Antioxidants (such as glutathione, Co-Q 10, folic acid, vitamin C and E and natural carotenoids) reduce the damage caused by these free radicals. If antioxidants are lacking and toxin exposure is high, toxic chemicals become far more dangerous. Some may be converted from relatively harmless substances into potentially carcinogenic substances.

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 will result in high levels of damaging free radicals being produced. Substances that may cause over activity (or induction) of the P- 450 enzymes: Caffeine, Alcohol, Dioxin, Saturated fats, Organophosphorus pesticides, Paint fumes, Sulfonamides, Exhaust fumes, Barbiturates

The family of P-450 enzyme systems is quite diverse, with specific enzyme systems being inducible by particular drugs, toxins or metabolites. It is this characteristic that has allowed the development of special tests to check the function of the various pathways – see liver tests. The substrate is the substance that is acted upon by the enzyme.

Phase Two – Detoxification Pathway

This is called the conjugation pathway, whereby the liver cells add another substance (e.g. Cysteine, Glycine or a sulphur molecule) to a toxic chemical or drug, to render it less harmful. This makes the toxin or drug water-soluble, so it can then be excreted from the body via watery fluids such as bile or urine.

Major Phase II pathways include glutathione, sulfate, Glycine, and glucuronide conjugations. Individual xenobiotic and metabolites usually follow one or two distinct pathways. Again, this makes testing of the various pathways possible by challenging with known substances.

The conjugation molecules are acted upon by specific enzymes to catalyze the reaction step. Through conjugation, the liver is able to turn drugs, hormones and various toxins into extractable substances. For efficient phase two detoxification, the liver cells require sulphur-containing amino acids such as Taurine and Cysteine. The nutrients Glycine, glutamine, Choline and inositol are also required for efficient phase two detoxification. Eggs and cruciferous vegetables (e.g. broccoli, cabbage, Brussels sprouts, cauliflower), and raw garlic, onions, leeks and shallots are all good sources of natural sulphur compounds to enhance phase two detoxification. Thus, these foods can be considered to have a cleansing action. The phase two enzyme systems include both UDP-glucuronyl transferase (GT) and glutathione-S-transferase (GSH-T). Glutathione is the most powerful internal antioxidant and liver protector. It can be depleted by large amounts of toxins and/or drugs passing through the liver, as well as starvation or fasting. Phase II reactions may follow Phase I for some molecules or act directly on the toxin or metabolite.

A. Substrates of the Glycine pathway

Salicylates and benzoate are detoxified primarily through glycination. Benzoate is present in many food substances and is widely used as a food preservative. Many other substances are detoxified as well via the Glycine conjugation pathway. Patients suffering from xenobiotic overloads and environmental toxicity may not have sufficient amounts of Glycine to cope with the amount of toxins they are carrying.

B. Substrates of the sulfation pathways

Neurotransmitters, steroid hormones, certain drugs such as Acetaminophen (also known as paracetamol), and many xenobiotic and phenolic compounds.

C. Substrates of glucuronidation

Polycyclic aromatic hydrocarbons, steroid hormones, some nitrosamines, heterocyclic amines, some fungal toxins, and aromatic amines. It also removes “used” hormones, such as estrogen and T4 (thyroid hormone) that are produced naturally by the body.

Toxic Overload
If the phase one and two detoxification pathways become overloaded, there will be a build up of toxins in the body. Many of these toxins are fat soluble and incorporate themselves into fatty parts of the body where they may stay for years, if not for a lifetime. The brain and the endocrine (hormonal) glands are fatty organs, and are common sites for fat-soluble toxins to accumulate. This may result in symptoms of brain dysfunction and hormonal imbalances, such as infertility, breast pain, menstrual disturbances, adrenal gland exhaustion and early menopause. Many of these chemicals (e.g. pesticides, petrochemicals) are carcinogenic and have been implicated in the rising incidence of many cancers.

Rarely does anyone think about the liver, which seems incredible to me because it is such a powerful organ and is easily improved. Indeed the simplest and most effective way to cleanse the blood stream and thus take the load off the immune system is by improving liver function. An example of the phase one pathway is the Cytochrome P-450 mixed function oxidase enzyme pathway. These enzymes reside on the membrane system of the liver cells (called Hepatocytes).

  • An Approach to Medical Detoxification:
  1. Begin by cleaning out the colon.
    1. In the presence of slow colonic motility, many of the hepatic excretory products are reabsorbed by the small bowel.
    2. This can be accomplished with a combination of castor oil, enteric coated aloe, flax seed oil.
  2. Decrease viscosity of biliary and pancreatic fluids.
    1. This can be accomplished with oral NAC, guaifenesin.
  3. Purge the gall bladder.
    1. This must be undertaken carefully, as to prevent a ‘gall bladder attack.’
    2. Silymarin combined with curcuminoids is effective for this.
  4. Then, it is safe to begin influencing hepatic function.
    1. The best approach is to use a combination of agents, here.
    2. NAC, Curcuminoids, L-Theanine, Glutathione, Glycine, and others are used in combination.

There is no single product that is satisfactory for all patients and I have found no single product that performs the above actions sequentially. The process of liver detoxification should be undertaken over the course of a month or more, and it may need to be repeated, periodically, as patient condition & disease state might dictate.


As physicians, we dedicate a tremendous amount of time and energy studying drug-drug interactions. In so doing, we are looking at liver ‘detoxification’ from one, narrow viewpoint. We will recommend, prescribe or administer prescription medications, in the belief that only prescription medications can cure, treat, maim or kill.

In reality, for every medication that we prescribe, nature provides tens of thousands of environmental chemicals that have the potential to do well and harm. Oxygen can maintain life or cause disease. Ingestion of the naturally occurring substance, alcohol, can cause demonstrable metabolic damage, entirely without prescription. Nicotine is one of the most toxic substances found in nature.

Too much or too little sugar, salt, nitrogen, carbon dioxide will result in dysfunction. Why is it such a stretch of the imagination to believe that other substances found in nature have properties that can be of benefit to your patients?

At this time, our patients are seeking knowledgeable professionals to assist them in finding ‘natural’ approaches to health promotion and disease management.

About David S Klein, MD 149 Articles
David S. Klein, MD, FACA, FACPM was born in Washington, DC, and was raised in Chevy Chase, Maryland. He completed his undergraduate education at the University of Maryland with degrees in Chemistry and Psychology. Medical School was completed at the University of Maryland at Baltimore, followed by Internship in General Surgery at the University of North Carolina and Residency in Anesthesiology at the Duke University, Durham, North Carolina. Dr Klein has been practicing medicine since 1983, concentrating in Pain Medicine, Minimally Invasive Medicine and Surgery, and Neuroendocrinology. Earning Board Certification in Anesthesiology, Dr. Klein was elected Fellow in the American College of Anesthesiology, and he was elected Fellow in the American College of Pain Medicine. He is currently an adjunct Associate Professor at the University of Central Florida, School of Medicine. He has focused his private practice on treating patients with hormone imbalance issues, nutritional deficiency related medical problems as well as pain related issues and impairment. With a highly-complex, CLIA licensed laboratory in-house, he has been able to provide rapid-turn around analysis efficiently and cost-effectively. Lecturing extensively nationally as well as internationally, Dr. Klein has authored many articles on topics relating to pain, injury and nutritionally modulated illness. His radio show, “Pain Free Living,” received top ratings during the 6 years it was on the air. Currently practicing in Longwood, Florida, Dr. Klein practices entirely in the office setting.