Environmental Pressures Require Balanced Purification & Detox Support
Every day, the human body is exposed to endogenous and environmental toxins and toxicants. Common toxins and toxicants include heavy metals (e.g., lead, mercury), chemicals used in agriculture and manufacturing (e.g., pesticides, dioxins), and biotoxins (e.g., bacterial endotoxin). When not eliminated by the body’s natural detoxification system, toxins and toxicants can accumulate in organs and tissues rich in fat such as adipose and brain tissues where they disrupt normal cellular processes, with the potential to cause disease. Supporting detoxification through diet is an essential component of a healthy lifestyle. In fact, an evolving evidence base describes the dependence of the body’s natural metabolic detoxification system on proper nutrition, including specific foods and nutrients.
The results of these numerous studies suggest multiple benefits to a whole-food and plant-based diet in support of detoxification. This monograph describes the current understanding of how diet and detoxification interact and what specific foods can enhance toxin and toxicant removal from the body.
TOXINS AND THEIR EFFECTS ON THE HUMAN BODY
Toxins are harmful compounds made by bacteria, plants, or animals, whereas toxicants are compounds made by humans or introduced to the environment by humans; for simplicity, we will use the term toxin for both categories. Toxins are everywhere in modern life. Toxic substances such as arsenic, cadmium, lead, and mercury can be found in drinking water, foods, consumer products, and other sources. Toxins are also present in molds and environmental allergens, pesticides (especially older pesticides), and organic pollutants (e.g., dioxins, polychlorinated biphenyls, polyfluorinated stain repellents, nonstick compounds, solvents and other volatile compounds, and organochlorine chemicals).
Most toxins are lipophilic and readily cross cell membranes, where they can disrupt normal cellular functions. Among other adverse actions, toxins can bind to proteins, inhibit enzyme function, and interact with DNA.
Because they are lipophilic, toxins tend to accumulate in tissues rich in fat such as adipose tissues, liver, and brain.
Evidence suggests that inadequate clearance of toxins can play a role in the development of obesity, cardiovascular disease, neurocognitive conditions, immune dysfunction,4 chemical intolerance, and reproductive and developmental conditions. The cost of exposure to toxins is staggering. One conservative estimate of the cost of environmental diseases in children (e.g., lead poisoning, methylmercury exposure, asthma, etc.) totaled $76 billion in 2008. Given these potentially adverse effects and costs, the goals of healthy living now include minimizing exposure to toxins and enhancing metabolic detoxification processes. ENDOGENOUS DETOXIFICATION MECHANISMS The human body uses a well-described metabolic system to eliminate toxins. This detoxification system governs the mobilization, biotransformation, and excretion of toxins. Because most toxins are lipophilic(지방친화적) and not easily transported through the circulation, the initial steps of metabolic detoxification convert lipidsoluble toxins to water-soluble compounds by first activating and binding the toxin to another molecule or moiety, such as an amino acid, methyl group, or glutathione.
The transformed hydrophilic toxins can then be eliminated mainly via urine or feces. The metabolic detoxification process follows 3 discrete phases; the first 2 phases occur primarily in the liver( The phases of metabolic detoxification in the liver. Numerous nutrients
support efficient phase I and II conversion of toxins from lipophilic to hydrophilic to
enhance elimination in the urine or feces.). Throughout all phases, the detoxification system is highly dependent on proper nutritional support for optimal function.
Phase I: Bioactivation Phase I reactions are catalyzed by a variety of enzyme families, most notably the cytochrome P450 (CYP450) superfamily of enzymes. However, the CYP450 superfamily is responsible for the biotransformation of the majority of toxins, including xenobiotics, steroid hormones, and pharmaceuticals.9 The CYP450 enzymes are membrane-bound and located primarily in the liver, but are also present in the kidneys, lungs, and enterocytes, among other sites. They are responsible for the oxidation, peroxidation, and reduction of a wide range of endogenous and exogenous substrates.10 Genetic polymorphisms are common in CYP450 enzymes, contributing to inter-individual variability in enzyme expression and function.9 In Phase I of the biotransformation process, CYP450 enzymes add a reactive group (e.g., hydroxyl, carboxyl, or amino group) through oxidation, reduction, and/or hydrolysis reactions.10 Because these reactions result in the formation of reactive oxygen species, they have the potential to cause oxidative damage to cells.9 Furthermore, the resulting activated toxin, because of the new reactive site, can readily bind to other molecules, such as DNA or proteins, and therefore may be more hazardous to cells than the original toxin. The reactive intermediate toxins are considered more toxic than the parent compounds and must be rapidly neutralized to prevent oxidative damage to cells.
Phase II: Conjugation The results of phase I reactions are activated toxins (aka intermediate substances) that are more hydrophilic (watersoluble). In phase II, the intermediate substances created during phase I are conjugated with other compounds to further enhance the hydrophilicity of the modified toxin (Table 1).9 Compounds conjugated during this phase include glucuronic acid (via glucoronyl transferases), sulfate (sulfotranferases), glutathione (glutathione transferases), amino acids (amino acid transferases), acetyl groups (N-acetyl transferases), and methyl groups (N- and O-methyltransferases).9,11 These reactions further increase the hydrophilicity of the toxin, allowing for excretion in bile or urine. As with the CYP450 enzymes, genetic polymorphisms can affect the expression and activity of phase II enzymes.
Phase III: Transport or Elimination Phase Phase III of detoxification is mediated by transmembranespanning proteins that transport modified toxins out of cells and into the circulation. Because the toxins have been made hydrophilic through phase I and II reactions, they can be carried by the circulation to the kidneys for elimination in urine or the bile for excretion in feces. One variable that can affect the elimination of toxins is the urinary pH. For example, increasing urinary pH (i.e., alkalinization) increases the urine elimination of herbicides such as methylchlorophenoxyproprionic acid 2,4-dichlorophenoxyacetic acid.13 In fact, the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists issued a joint position paper on urine alkalinization, in which the authors noted that raising urine pH can increase the elimination of toxins such as chlorpropamide, diflunisal, fluoride, mecoprop, and many others.
Balancing Methylation Process Supports a Balanced Detox Program
Methylation is the transfer of one carbon methyl group from one molecule to another that either activates or deactivates that molecule. It is the process by which our epigenetics regulate gene expression. This single carbon metabolic process is mediated by enzymes such as methyltetrahydrofolate reductase (MTHFR), catechol-O-methyltransferase (COMT), and cystathione beta-synthase (CBS). Each person’s genetic fingerprint in the form of single nucleotide polymorphisms (SNPs) dictates how efficiently these enzymes work.