We are exposed to a great number of xenobiotics during the course of our lifetime, including a variety of pharmaceuticals and food components. Many of these compounds show little relationship to previously encountered compounds or metabolites, and yet our bodies are capable of managing environmental exposure by detoxifying them. To accomplish this task, our bodies have evolved complex systems of detoxification enzymes. These enzyme systems generally function adequately to minimize the potential of damage from xenobiotics. However, much literature suggests an association between impaired detoxification and disease, such as cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Therefore, accumulated data suggests an individual's ability to remove toxins from the body may play a role in etiology or exacerbation of a range of chronic conditions and diseases.
The detoxification systems are highly complex, show a great amount of individual variability, and are extremely responsive to an individual's environment, lifestyle, and genetic uniqueness. This review of the detoxification systems is meant to whet the appetite for a more in-depth look at detoxification and, as such, it may raise more questions than it answers.
Many challenges to this system - a leaky gut, repeated exposure to food-borne toxic chemicals, environmental pollutants, bacterial endotoxins, and other substances - can increase the detoxification burden. This overload can lead to greater production of free radicals and damage to many body systems. Assessing multiple path-ways with challenge substances provides clinical information about individuals with imbalanced detoxification.
Long term exposure to environmental pollutants and continued affronts to the detoxifying systems may lead to oxidative stress, high levels of P-450 activity, and reduced capacity for Phase II conjugation reactions. This can result in accumulation of the toxic compounds, damage to essential fatty acids, impairment of oxidative phosphorylation, and reduced energy production.
Patients suffering from toxic burdens may experience a wide range of symptoms, among them fatigue and poor tolerance for exercise. These processes have been postulated to be a central factor in the
development of Chronic Fatigue Syndrome (CFS). A recent study reported that many CFS patients had disordered liver detoxification
ability and showed signs of increased toxic exposure. Buist suggests that CFS may be a result of xenobiotic or toxin exposure.
All ingested and microbially-produced toxins are presented to the first-pass clearance system. First-pass clearance involves the biotransformation and clearance of a chemical from the body before
it reaches the systemic circulation. This clearance may take place in several organ tissues including the intestinal mucosal wall and the liver.
The liver is the body's primary detoxifying organ. Here, detoxification is carried out in two related processes known as Phase I and Phase II. Phase I serves to biotransform substances through oxidation, reduction or hydrolysis, using the cytochrome P450 mixed-function oxidase enzymes. This process increases the solubility of molecules and prepares them for Phase II reactions which will further increase their solubility.
The Phase I reactions are necessary for detoxification, but the resulting production of reactive oxygen species can at times be very damaging. Thus, the liver needs to be able to generate oxidation capacity when needed, yet at the same time generate no more than what is needed. Perhaps this is why Phase I systems are inducible by different compounds.
In Phase II, conjugation reactions add a polar hydrophilic molecule to the metabolite or toxin, converting lipophilic substances to water-soluble forms for excretion and elimination. Phase II reactions may follow Phase I for some molecules or act directly on the toxin or metabolite. Major Phase II pathways include glutathione, sulfate, glycine, and glucuronide conjugations. Individual xenobiotics and metabolites usually follow one or two distinct pathways. While the modification of Phase I and II enzyme activities has its basis in the research setting, there is growing appreciation of the clinical applications of such strategies. Although exhaustive clinical studies have yet to be performed, we have the biochemical and logical basis upon which to recommend interventions in order to help patients with evidence of chemical sensitivity or high exposures to toxic compounds. It should be noted, however, that nutritional modification of the P-450 and/or conjugation pathways has strong potential to change drug metabolism. Due to this potential metabolic impact, practitioners should use caution and awareness when recommending such strategies in patients taking prescription medications.
There are specific nutritional and homotoxicological products used in the liver detoxification process.