References In her 1962 groundbreaking book Silent Spring, Rachel Carson wrote: “For the first time in the history of the world every human being is now subjected to contact with dangerous chemicals, from the moment of conception until death.” Of course humans have always been exposed to potentially harmful chemicals from plants and other sources, but Carson’s point is well taken. Modern living exposes all of us to an unprecedented number of chemicals on a daily basis. This includes environmental toxins such as heavy metals, pesticides, industrial compounds and chemical byproducts, medications, cosmetic additives, inorganic chemicals and much more. These chemical substances that are foreign to the biological system are referred to as “xenobiotics.” The good news is that the body was designed to detoxify and excrete xenobiotics. The bad news is that the body may not always be equipped to handle the volume of modern environmental pollutants and toxic substances. This problem may be exacerbated by the fact that the refining of many of our foodstuffs has caused them to provide considerably less of the nutrients that are essential to the detoxification process.1,2 Ramifications of Toxic Overload The ramifications of toxic overload can vary from one individual to another. One possible ramification is multiple chemical sensitivities (MCS). Individuals with MCS experience various symptoms in response to being exposed to certain types of chemicals, primarily (but not limited to) those of petroleum and coal-tar derivation. There are many possible symptoms including headaches, fatigue, depression, and an overall feeling of malaise and illness. Consistent, long-term exposure to certain chemicals at home or in the workplace leads to intolerance in some individuals and, from there, into MCS. For many MCS sufferers, a sensitivity reaction will occur when exposed to even minute amounts of the offending chemicals, which, in turn, can lead to severe symptoms.3 Of course an individual may suffer from toxic overload without having full-blown MCS. In fact, the most common symptom of toxic overload is probably fatigue. Other common symptoms include headache, muscle and joint pain, irritability, depression, mental confusion, gastrointestinal and/or cardiovascular irregularities, flu-like symptoms or allergic reactions including hives, stuffy or runny nose, sneezing and coughing.4 Furthermore, some researchers have suggested that toxic overload may contribute to autoimmune diseases including inflammatory and rheumatoid arthritis,5,6 and neurological diseases such as Alzheimer’s and Parkinson’s.7 The question of how to deal with toxic overload has a multipart answer that includes following a healthier diet and reducing exposure to xenobiotics. The books Multiple Chemical Sensitivity (New Harbinger Publications Inc.) and Staying Well in a Toxic World (The Nobel Press) provide good direction on how to do this. Another part of the answer is to help the liver become more proficient at detoxification. Liver Detoxification Water-soluble toxins can pass through our bodies unchanged and be eliminated in the stool, sweat or urine. Fat soluble toxins, however, cannot be excreted without undergoing metabolic transformation (detoxification) in the liver into water-soluble compounds. Liver cells have sophisticated mechanisms to break down toxic substances. These include both endogenous (produced by the body) and exogenous (obtained from the environment) substances. Every drug, chemical, pesticide and hormone is broken down or metabolized via detoxification pathways in the liver called Phase 1 and Phase 2. Phase 1 utilizes cytochrome P450 enzymes produced in the liver. These enzymes initiate reactions that generally involve exposing or adding a “functional group” to the toxic molecule. This process of making the molecule more reactive is required as the first step in increasing its water solubility for excretion. Some chemicals are already highly reactive and they have functional groups, so they can bypass Phase 1 and go right to Phase 2. The majority, however, first need Phase 1 activation. Unfortunately, Phase 1 enzymatic reactions generate free radicals, increasing the potential for oxidative damage.Phase 2 involves the coupling or conjugation of a water-soluble substance that is endogenously produced or sourced by the body to the toxin. This makes the toxic molecule more water soluble and, therefore, less toxic. If the molecule is large, it is then excreted via the bile; otherwise, it is excreted in the urine. Now that we’ve briefly examined the process of liver detoxification, let’s take a look at how we can use dietary supplements to support and promote liver detoxification.Specialty Compounds Certain amino acids are used in Phase 2 as the water-soluble substance that is conjugated (attached) to the toxic molecule. These amino acids include glycine, taurine and glutamine.8 Clinically, supplementation with these amino acids has shown great benefit for patients with toxic overload, especially when body cleansing was undertaken at the same time.9 Likewise, methyl groups also act as conjugating agents in phase 2.10 Trimethylglycine (betaine) is a donor of methyl groups, and may be useful as such in biochemical reactions in the liver.11 N-acetylcysteine (NAC), a combination of the amino acid L-cysteine and an acetyl group, is the precursor to glutathione, the body’s predominant endogenous antioxidant.12 NAC stimulates glutathione synthesis and promotes liver detoxification, as well as acting as a powerful scavenger of free radicals.13,14 NAC has been used for treating poisonings with acetaminophen, heavy metals and toxins including carbon tetrachloride, paraquat and interferon.15 Another Phase 2 pathway is the glucuronidation pathway. In this pathway, glucuronic acid is attached to certain toxins as well as hormones such as estrogen to facilitate their removal by excreting them via bile into the intestinal tract. The problem is that betaglucuronidase, a bacterial enzyme found in the intestines, can break the bond that attaches the glucuronic acid to the toxin releasing it back into the body. Fortunately, the use of D-glucarate appears to inhibit beta-glucuronidase from breaking the bond in the first instance.16 D-glucaric acid is a natural substance found in many fruits and vegetables such as apples, grapefruit, broccoli and Brussels sprouts. Calcium D-glucarate is the calcium salt of D-glucaric acid and is the form typically used in dietary supplements. In a study from the University of Texas M.D. Anderson Cancer Center, calcium D-glucarate inhibited beta-glucuronidase by 57 percent in the blood, 44 percent in the liver, 39 percent in the intestines and 37 percent in the lungs.17 Such an inhibition of beta-glucuronidase may do much to protect the action of the glucuronidation pathway. Botanical Support In herbal medicine, milk thistle (Silybum marianum) is arguably the premium liver herb. The active components in milk thistle are the flavonoids collectively called silymarin, and the majority of related research has been conducted on this component. Silymarin has long been recognized for its ability to benefit people with liver disorders, including hepatitis18,19,20,21 and cirrhosis.22 Silymarin also protects against glutathione depletion,23 and increases liver glutathione status.24 Since glutathione is one of the primary conjugating agents in Phase 2, this is a significant contribution by milk thistle in supporting detoxification by the liver.25 In addition, milk thistle provides liver protection by stabilizing liver cell membranes. It alters the structure of the outer cell membrane in such a way as to prevent toxins from penetrating into the interior of the cell. Milk thistle and silymarin may increase the regenerative ability of liver cells,26 and prevent liver damage from prescription medications.27 Turmeric (Curcuma longa) is a bright yellow, ancient spice and a traditional remedy that has been used as a medicine, condiment and flavoring based on records dating back to 600 BC. Turmeric and its curcuminoids also exhibit strong antioxidant activity,28 enhance cellular resistance to oxidative damage,29 and enhance the body’s natural antioxidant glutathione levels.30 Turmeric has also been found to have hepatoprotective (i.e., liver-protective) properties against a variety of liver-toxic chemicals and drugs.31,32,33,34Green tea (Camellia sinensis) compounds increase both Phase 1 and Phase 2 enzyme activities35 and may have liver protective properties.36 In addition, green tea has been shown to block chromosomal (DNA) damage from chemicals in cigarette smoke.37 Perhaps not surprisingly, green tea polyphenols are associated with a reduced risk of certain cancers in humans.38 The Asian adaptogenic botanical schizandra (Schizandra chinensis) also appears to have significant value for the liver. The lignans in schizandra appear to activate the enzymes in liver cells that produce the antioxidant glutathione, enhancing Phase 2 detoxification reactions.39 Furthermore, in vitro studies have shown that constituents of schizandra decrease the mutagenicity of mutagenic toxin benzo(a)pyrene (BaP).40 Schizandra also induces Phase 1 detoxification enzymes, yet has not been shown to cause any drug interactions.41 In addition, Chinese researchers report schizandra has helped patients with chronic viral hepatitis.42,43 Garlic also appears to induce both Phase 1 and Phase 2 enzymes.44,45 In addition, aged garlic extract may increase the glutathione level and glutathione related enzymes that aid in detoxifying the body.46,47,48,49 Research has also suggested that garlic extract may help to protect the body from heavy metal poisoning.50 When garlic extract was combined with red blood cells it prevented lead, mercury and aluminum from destroying them. Without the garlic extract, these heavy metals ruptured the red blood cells. Another fragrant herb, rosemary, contains carnosol, an antioxidant that inhibits bioactivation of BaP and induces glutathione-S-transferase (a detoxification enzyme) and other important phase 2 enzymes.51,52 Animal research suggest rosemary components may significantly increase Phase 2 liver enzymes, protecting the liver and stomach from carcinogenic or toxic agents.53Bladderwrack (Fucus vesiculosus) is a type of brown algae that grows on the northern coasts of the Atlantic, Pacific and Baltic. In research, bladderwrack has been shown to consume and metabolize toxic polycyclic aromatic hydrocarbons, particularly BaP.54 Bladderwrack has been shown to absorb certain heavy metals such as tin.55The dietary supplements discussed in this article are certainly not the only natural compounds capable of supporting and facilitating the liver’s detoxification process. Compounds from citrus fruit and the Brassica or cruciferous group of vegetables (e.g., cabbage, Brussels sprouts, broccoli, etc.), as well as the dietary supplement alpha lipoic acid are examples of other effective detoxifying agents.56 Nevertheless, the compounds listed can be effective adjuncts to a program for detoxification. Although the focus of this article is on the use of dietary supplements that may help promote liver detoxification, it should be understood that toxic overload should be treated with a comprehensive approach that also includes adapting to a healthier diet and reducing exposure to xenobiotics. Furthermore, since there can be side effects associated with a serious program of detoxification, it should generally be attempted with the help of a health care professional who is knowledgeable about the process. Gene Bruno is on the administrative staff and faculty of Huntington College of Health Sciences (HCHS). HCHS is an accredited distance learning institution offering undergraduate and graduate degrees, as well as a diploma program in nutrition. For more information, visit www.hchs.edu or call (800) 290-4226.
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