Detoxification Circuit Dysfunction – Part 1

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM; Carrie Lam, MD

Symptoms of a dysfunctional detoxification circuitThe body’s overall de-stress mechanism, from a functional perspective, is carried out largely by the NeuroEndoMetabolic (NEM) Stress Response apparatus and the detoxification circuit. There are six total circuits within this apparatus, each comprising multiple systems and organs. They all work in unison when stress arrives at the doorstep to ensure internal homeostasis is continually maintained.

Relying on the hypothalamus-pituitary-adrenal (HPA) hormonal axis as the main conduit for relieving stress is an incomplete model from a functional perspective. The HPA axis plays an important part and is most prominently deployed when stress is mild or moderate. However, the body has additional mechanisms in place when stress is severe or perceived to be a threat to survival. These are activated at different times as the body sees fit. When combined with the HPA axis, these circuits become a fine-tuned orchestra. Thus far, it has worked well and provided for the survival of our species.

There are 6 functional circuits, each comprised of multiple organs and systems. They are all part of the body’s NeuroEndoMetabolic (NEM) Stress Response System that regulates stress from a global perspective. One of the most important circuits is the detoxification circuit. It is comprised of the liver, the extracellular matrix (ECM), and the immune system. Together, they get rid of excessive, unwanted, reactive metabolites that come from stress. Remember that stress can be physical or emotional. It represents an exertion on the body that requires energy expenditure to normalize. When this circuit is working well along with other circuits, stress is automatically resolved in the background without you knowing it.

However, if there is detoxification circuit dysfunction (and it is not functioning as it is supposed to be), clinical symptoms can be devastating.

Reactive Metabolites

To understand how the detoxification circuit works, we first have to understand what metabolites are. A metabolite is defined as a product of metabolism. Each substance, once it enters the body, needs to be broken down into smaller pieces as part of the excretion process to rid the body of unwanted by-products. Toxic substances the body receives from daily living include hormone-laced food, polluted air, stress, medications, and unclean water. Excessive metabolites are toxic to the body.

Fortunately, the body has a built-in detoxification mechanism to convert natural compounds into inert metabolites prior to excretion. The liver is the primary organ responsible. Most toxins are neutralized inside the liver by a two-step process. Phase 1 makes fat-soluble toxins into water-soluble metabolites. Phase 2 takes the metabolites from phase 1 and inactivates them. The liver is also a depot for many immune cells, such as lymphocytes, which are ready to be called into action to neutralize pathogens.

Problems usually come when foreign or synesthetic compounds, such as pesticides, pollutants, medications, and herbs, are introduced in excess. The body does not have a built-in detoxification mechanism robust enough to do the job completely, especially when it is weak. Metabolites may not be removed properly or quickly enough. Some of these metabolites are not inert but active. Active metabolites are also called reactive metabolites because they react with other things in the body and can become toxic. In most cases, the build-up of chemically reactive metabolites is temporary, and the body gets rid of them after multiple passes through the system. In some cases, such as with toxic metals like mercury, the toxin never leaves the body on its own.

Triggers for excessive metabolites include:

The detoxification circuit can become deregulated by staying up at night

  • Staying up at night excessively
  • Physical trauma leading to muscle breakdown
  • Excessive exercise
  • Adrenal crashes
  • Menstrual cycle turbulence
  • Hormonal imbalance
  • Excessive heat
  • Gastric slowdown
  • Catabolic state
  • Chronic and stealth infections and coinfections such as candida, Lyme, Epstein-Barr virus (EBV), Small intestine bacterial overgrowth (SIBO), H. pylori
  • Excessive methylation
  • Excessive alcohol
  • Excessive pollution, including from air, water, and chemicals from processed food
  • Excessive chelation and IV nutritional therapy
  • Aggressive fasting protocols
  • Improper use of natural compounds, including glandulars and herbs
  • Prescription medications, including painkillers, antidepressants, thyroid medications, proton-pump inhibitors, immunosuppressants
  • Street and recreational drug use, including medical cannabis
  • Over aggressive chiropractic manipulation or acupuncture
  • Exposure to changes in ambient temperature that the body cannot handle
  • Exposure to changes in weather conditions, especially humidity
  • Exposure to excessive EMF such as from cell phones or computer monitors
  • Over aggressive detoxification modalities such as liver flushes and enemas
  • The time before and after menstruation, especially in people with existing estrogen dominance
  • Eating hard to digest food, such as eggs for some blood type O people
  • Long-term ingestion of prescription medications such as steroids, sleep medications, certain antidepressants, benzodiazepines, and proton pump inhibitors

As you can see, almost no one living in the modern, stressful world can escape having reactive metabolites. The degree of damage depends on the quantity and frequency of exposure. The body’s built-in detoxification circuit is designed to get rid of unwanted metabolites to a certain degree. If they are not properly and promptly removed, the risk of accumulation in the body grows over time.

As mentioned earlier, metabolites can be inert or reactive. Reactive metabolites are the ones that cause most of the damage inside the body. The more unwanted reactive metabolites we have, whether from food, stress, medication, or nutritional supplements, the heavier the burden is on the body, especially the liver, to get rid of them. While those who are healthy have no problem accomplishing this task, the same cannot be said for those who have chronic illnesses or a weak constitution. They are most vulnerable to metabolite buildup.

Reactive metabolite overload (RMO) is a term used to describe a body that has excessive reactive metabolites to the degree that the detoxification circuit becomes dysregulated, and clinical symptoms start to surface.

RMO and Detoxification Circuit Dysfunction

When the body is in a state of RMO, it can trigger or lead to liver congestion, ECM pollution, and immune system hyperactivation. This triple overload can create a perfect storm that leads to detoxification circuit dysfunction.

Let us see how this happens. Remember that the body is a closed system. Homeostasis can be disrupted by accumulation of excessive metabolites beyond the body’s ability to promptly clear. All metabolites, inert or reactive, circulate within the entire body continuously until excreted through the lungs, skin, bowel, or kidneys. While in transit, one of the first systems to experience toxic effects is the extracellular matrix, the ECM.

Along with liver congestion and immune system hyperactivation, ECM pollution can lead to detoxification circuit dysfunctionThe ECM comprises spaces outside of each cell and is an important highway network upon which metabolites travel from one part of the body to another. Excessive metabolites within the ECM will invariably lead to ECM pollution. Like a highway with too many cars, the speed of flow slows down and more exhaust enters the air. The result is more pollution. Also, the more cars on the highway, the higher the chance of accidents. If the volume of cars and speed of flow is not normalized, the ECM can become congested, aggravating the system even more. It becomes a vicious cycle. Because the ECM is also responsible for intercellular messaging, disruption of transmission can occur, leading to defective signal transfer between cells.

Reactive metabolites eventually and invariably will be transported to the liver for breakdown. Inside the liver, this job falls mostly on the cytochrome P450 detoxification system. Excess reactive metabolites then become a burden to the liver. The more metabolites received, the harder the liver has to work to remove them.

The intended result is to create more inert metabolites, which are harmless, rather than reactive metabolites, which can be harmful. Thus, as the liver is put on overdrive, the body is flooded with more downstream metabolites, both inert and reactive. Unfortunately, inert metabolites also have to be eliminated. They may not be toxic, but nevertheless, they can contribute to congestion and slow the flow of the ECM. As the velocity of flow within the ECM reduces, toxic, reactive metabolites within can cause localized damage to the immediate extracellular space, damaging the extracellular scaffolding necessary for organ structural integrity.

All metabolites, from a variety of sources, eventually converge and travel within the ECM highway system to the kidneys for excretion after processing by the liver. Metabolites not cleared immediately recycle within the body, causing systemic inflammation and immune system activation.

RMO, therefore, is undesirable. It sets the body up for multiple insults, leading to what is known as a retoxification reaction. On top of this, the liver can become congested as excessive inert and reactive metabolites accumulate within from backflow due to EMC congestion. This can result in what is commonly known as ‘sluggish liver’. Localized hepatotoxicity can occur, damaging the already overworked liver. Collectively, this vicious cycle is a decompensatory cascade, between the ECM pollution and liver congestion, ultimately rendering the entire body toxic, like a septic pool or swamp. This is when the detoxification circuit becomes damaged and dysfunctional.

Immune System Hyperactivity

Along with the liver and the ECM, the immune system forms the third pillar of the detoxification circuit. The immune system is able to detect pathogens that may become active when the body is under stress. It can sense an increase in metabolites as the liver and the ECM become congested. To protect us, an inflammatory response is initiated to help neutralize any pathogens that may take this opportunity to surface. The detoxification circuit includes the immune systemThe immune system’s job is to attack and neutralize a myriad of active and potential pathogens simultaneously. Flare-ups of co-infectious states (such as H. pylori and Lyme Disease) and chronic pathogens (such as candida and EBV) will be automatically squashed if the immune system works properly. A properly working immune system will generate metabolites, much of it from pathogens that have been destroyed but still have to be cleared out of the body.

Laboratory tests indicative of an active immune system include elevated white blood cell count and CRP (C-reactive protein). Unfortunately, these tests can be elevated from a variety of sources and therefore is not very specific.

Aside from external pathogen-induced immune activation such as a flu or viral upper respiratory tract infection, or a sinus infection, it is important to note the following can also activate the immune response:

Food sensitivity. Eating a food you are sensitive to can cause inflammation and lead your immune cells to be activated.

Microbiome imbalance. The gut is a complete ecosystem on its own, perfectly maintained by beneficial bacteria. When this system is off balance, good, beneficial bacteria are replaced by foreign, non-beneficial bacteria, as it is for those with SIBO, gastric reflux, H. pylori, irritable bowel, inflammatory bowel disease, catabolic state, or gastric slowdown in advanced adrenal fatigue. Gastric assimilation becomes suboptimal. Foreign opportunistic bacteria and stealth viruses transition from a dormant to an active state. This causes the immune system to go into full throttle.

Increased intestinal permeability (leaky gut). When food particles cross the gastrointestinal mucosa, inflammation is triggered. Undigested foods are supposed to be inside the GI tract. When it enters hepatic circulation and the rest of the body, the immune system recognizes this as foreign and attempts to attack and neutralize it.

Heavy metal toxicity and chemical sensitivity. Environmental toxins are everywhere. It is impossible to escape if one lives in the urban world. Excessive toxins accumulating in the body trigger the immune system to rid the body of such unwanted material.

Chronic and stealth infections. We are exposed to a constant barrage of virus, fungi, bacteria, and protozoans. Some pathogens tend to stay with us for a long time in a dormant state. They become activated and flare up when your immune system is weak. These organisms include Borrelia burgdorferi, Babesia microti, Candida albicans, EBV, Cytomegalovirus (CMV), and many others.

Read Part 2

© Copyright 2017 Michael Lam, M.D. All Rights Reserved.

Detoxification circuit