The body’s organs of detoxification have evolved to handle a wide variety of toxins from both our internal and external environments. When we think of toxins, we often consider the synthetic chemicals and poisonous substances from the environment which have become associated with causing harmful effects in the body. However, toxins come from a variety of sources including our body’s own metabolic and cellular processes, as well as from our own bowel flora. These natural toxins, known as “endotoxins”, must be processed and safely eliminated through the body’s detoxification systems in much the same way as external chemicals, or “exotoxins” from the environment.
Although humans have become remarkably well adapted to processing a significant toxic load from our internal environments and from our air, food and water supply, we are continually being exposed to increasing amounts of commercial and industrial chemicals that are released into our environment each year, and this is placing an extraordinary demand on the liver. Some of these exogenous toxins include heavy metals, xenoestrogens, persistent organic pollutants, pesticides, fungicides, alcohol, as well as prescription and over the counter medications. Unfortunately, the long-term health effects of continuous, low-level exposure of multiple chemicals, simultaneously, remains poorly understood. However, it is well known that toxins cause damage in the body by various mechanisms, and understanding these mechanisms is important when looking at the clinical consequences of long-term toxin exposure.
Some of the main mechanisms by which toxins cause damage in the body include the formation of reactive oxygen species (ROS), direct damage to DNA and cell membranes, hormone disruption, and impaired metabolism. The good news is that the body’s detoxification systems are well equipped to neutralize a lot of these chemicals, and it can efficiently repair some of the damage that occurs on both a cellular and organ level. However, with this ever-increasing toxic burden, the body has a hard time keeping up, leading to improper elimination and the accumulation of toxic substances in cells and tissues.
There are six main organs that make up the body’s detoxification system, and these include the liver, kidneys, lungs, large intestine, skin and the lymphatic system. Out of all these organs, the liver is most talked about when it comes to “detoxification” and that is because it plays the crucial role of processing many chemical substances so that they can be safely eliminated from the body. The liver is the body’s largest internal organ and it is responsible for over 250 individual functions. In addition to playing a key role in detoxification, the liver is also involved in the metabolism of carbohydrates, fats and proteins and is responsible for the production, storage and processing of many substances.
Liver detoxification involves three complex phases, each with various types of biochemical reactions, and each requiring specific enzymes to properly and safely eliminate toxins from the body. Essentially, this complex process makes fat-soluble toxins more water-soluble and thus easier to excrete. In Phase I, known as the “cytochrome P450 enzyme system”, toxic substrates are converted into more biologically active and potentially more toxic metabolites. This phase requires many of the B vitamins including riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), folic acid, vitamin B12, as well as the antioxidant glutathione, flavonoids, phospholipids and various branched-chain amino acids. After phase I, Phase II, known as the “conjugated pathway”, modifies these intermediary metabolites making them even more water-soluble and available for excretion. Phase II pathways require the amino acids glycine, taurine, glutamine, N-acetylcysteine, cysteine and methionine. Phase III enzymes then release the metabolites from phase II by moving them from the liver’s cells into the extracellular environment for excretion into bile, faeces, urine, sweat, and breath.
The significance of such specific nutrient requirements is important since the liver can get backed up leading to difficulties eliminating toxic substances. If nutrients are not available to support these pathways, for instance if phase II is not working efficiently due to lack of key amino acids, then toxic metabolites from phase I cannot be properly eliminated and instead can cause further tissue damage through the formation of free radicals. Keep in mind that the body is also equipped to deal with these metabolites formed in phase I by producing antioxidants to neutralize reactive oxygen intermediates. However, many key antioxidants used by the liver must be obtained from the diet such as ascorbic acid (vitamin C), carotenes (Vitamin A), tocopherols (vitamin E), as well as minerals such as selenium, zinc, manganese and copper. This is why eating a diet rich in vitamins, minerals, amino acids and antioxidants is essential to ensure proper functioning of the liver’s detoxification pathways.
In addition to ensuring adequate nutrition for liver health, it is also important to understand that certain dietary, herbal and pharmaceutical substances can influence the detoxification process by promoting or inhibiting each pathway. Each phase can be either induced or inhibited by specific nutrients, antioxidants, herbs and pharmaceuticals. This complex process is the reason why some adverse reactions or interactions can occur between pharmaceutical and nutraceuticals. This is also why it is important to consult with a medical professional when combining prescription or over the counter medications and when adding in certain natural substances such as herbs and supplements.
To add to the complexity of this detoxification process, liver function is also influenced by our genes. We have genetic predispositions that determine the efficiency of the liver’s detoxification pathways, and some individuals have genetic predispositions that increase vulnerability to toxin damage. Research in the field of genetics is now showing that the liver enzyme systems responsible for metabolizing 20%-50% of all drugs has a wide range of function based on genetic variation. For instance, genetic variation between individuals can range from “poor” to “ultra-rapid” metabolic activity, which could influence the body’s capacity to detoxify certain drugs or metabolic substances.
Nutritional status and genetics are not the only important determinants of liver health. Other factors that further influence the liver’s detoxification capacity include underlying disease states, digestive function, smoking, alcohol consumption, exercise, sleep and stress. With all these factors playing into the intricate workings of the liver, and with the ever-increasing levels of toxins in our environment, it is important more than ever before to adopt a healthy lifestyle aimed at minimizing toxin exposure and supporting this very important organ. After all it is our largest, hardest working organ!
Bertin G, Averbeck D. Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie. 2006 Nov;88(11):1549-59.
De Rosa CT, Hicks HE, Ashizawa AE, et al. A regional approach to assess the impact of living in a chemical world. Ann NY Acad Sci. 2006 Sep;1076:829-38.
Limón-Pacheco J, Gonsebatt ME. The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutat Res.2008. Oct 8. Epup ahead of print.
Pizzorno JE, Ketzinger, J. Clinical Pathophysiology: A functional perspective. Mind Publishing, Coquitlam. 2012. Pp: 3.1-3.20.