Dr. Chris Shade

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Part 2 Back to Basics: Metals Testing

The human body is exquisitely designed with an internal system of detoxification pathways that eliminate substances harmful to our health, including heavy metals. However, the elevated exposure to heavy metals that many of us face today, combined with health conditions and genetic variations that impair detox, means that most of us could use extra detoxification support!

Heavy metals detoxification does not need to be a drawn-out, uncomfortable process. When you address inflammation and gut health and engage both the cellular and systemic routes of detoxification, you can seamlessly release heavy metals from your body without undue discomfort or the risk of redistribution. 

Phases of Detoxification

The liver is the “hub” of detoxification in your body. There are three phases by which the liver clears toxins. In phase I of detoxification, toxins are activated by enzymes into reactive intermediates. The enzymes utilized in this process are primarily CYP enzymes.

In phase II, chemical groups are conjugated to the reactive intermediates, making them more water-soluble so that they can be transported to the bile and urine for excretion. The glutathione pathway is particularly crucial in phase II detoxification of heavy metals.

In phase III of detoxification, conjugated toxins produced during phase II are transported from the blood to the liver and then from the liver to bile for excretion in the stool. Phase III utilizes multidrug-resistance associated proteins (MRP 1 and 2), OATP, and BCEP.1,2

Neglecting phase III while upregulating phases I and II prevents effective detox and may cause harm by increasing inflammation and redistributing heavy metals throughout the body.

Nrf2: The “Cellular Switch” for Detox

The nuclear factor erythroid 2-related factor pathway, referred to simply as Nrf2, is essential for heavy metals detoxification.3 Nrf2 is a “cellular switch” that turns on cellular production of antioxidants involved in phases I and II of heavy metals detoxification. The Nrf2 system is naturally upregulated in response to mercury exposure but may require extra support in those with heavy body burdens of metals and compromised detox pathways.4

Many natural compounds have been found to upregulate Nrf2. Some of these compounds are actually mild “toxins” that trigger Nrf2 activity, resulting in antioxidant production and a net benefit for your health. One of the direct benefits of Nrf2 upregulation is increased glutathione production, essential for heavy metals detoxification.

Prerequisites for Detox: Inflammation and Gut Health 

To safely and efficiently detoxify heavy metals, it is crucial that you address inflammation and gut health both before and during your detox.

Inflammation

Chronic inflammation is a critical barrier to successful heavy metals detoxification. Inflammation amplifies mercury toxicity by uncoupling phases I and II of detoxification.5 Quenching inflammation is thus a prerequisite for successful heavy metals detoxification.

Gut Health

Increased intestinal permeability (aka “leaky gut”) and gut dysbiosis release endotoxin, a pro-inflammatory compound found in the cell walls of Gram-negative bacteria, into the systemic circulation. Once in the circulation, endotoxin provokes inflammation and has been found to enhance the toxicity of heavy metals.6 Endotoxin also downregulates the activity of cellular transporters involved in phase III detoxification and blocks AMPK, a cell signaling pathway that regulates inflammation and the detox capacity of the liver. 7,8 Repairing leaky gut and gut microbiome imbalances is thus crucial for the successful detoxification of heavy metals.

To halt the vicious cycle of leaky gut and heavy metals toxicity, you’ll first need to remove or limit factors that increase intestinal permeability, including:

  • Alcohol 9
  • NSAIDs 10: Instead of NSAIDS, try CBD for supporting inflammatory balance.
  • Bacterial overgrowth and gut infections 11,12
  • Celiac disease and non-celiac gluten sensitivity 13
  • Psychological stress 14
  • High-intensity, long-duration exercise 15
  • Glyphosate, a common pesticide used on non-organic food 16
  • Mercury 17

Nutraceuticals for Metals Detoxification

Glutathione

The glutathione system is critical for heavy metals detoxification. Glutathione is a crucial mediator of phase II detox, forming complexes with heavy metals and preparing them for excretion. Glutathione enhances phases II and III of detoxification. Nrf2 activation increases glutathione levels, but direct supplementation is also beneficial. In cell culture studies, liposomal glutathione has been demonstrated to be 100 times more effective for boosting levels of this critical antioxidant than non-liposomal glutathione.18

Bile Flow Promoters

Bile flow is an essential but often overlooked component of heavy metals detoxification. Bile salts enhance the expression of MRP proteins involved in phase III detox.19 Milk thistle, a highly-valued bitter in traditional herbal medicine, stabilizes phase III transporters in the canalicular membranes of liver cells, assisting liver detoxification.20 Gentian and myrrh induce MRP2 and BCEP expression, enhancing bile flow and liver-protective properties.21,22

Nrf2 Upregulators

Activation of Nrf2 is key for mobilizing phases II and III of detoxification. R-lipoic acid is an antioxidant that upregulates Nrf2 and regenerates other antioxidants, including vitamins C, E, and glutathione.23 DIM is a natural compound found in cruciferous vegetables that, in addition to upregulating Nrf2, balances immune system activity.24 This is crucial for detoxification because chronic inflammation hinders successful detox.

AMPK Activators

AMPK is a cell signaling pathway that regulates metabolic health, intestinal permeability, mitochondrial function, and detoxification. AMPK activators help seal up leaky gut, creating a healthy foundation for heavy metals detoxification.25

A variety of natural compounds activate AMPK, supporting the integrity of the gut barrier and detoxification, including quercetin, luteolin, DIM, R-lipoic acid, and milk thistle.26,27,28,29 Quercetin and luteolin are also mast cell stabilizers, while DIM inhibits inflammatory cytokine release in response to endotoxin; together, these nutraceuticals balance inflammation during detoxification.30,31,32

Phosphatidylcholine

Cell membrane phospholipids are subject to damage by heavy metals. Liposomal nutraceuticals are particularly beneficial for heavy metals detoxification because they are rich in phospholipids that can be used to repair damaged cell membranes and promote bile flow. 33

Binders

The enterohepatic circulation is the process by which bile acids, bilirubin, and conjugated toxins from the liver to the bile, followed by reabsorption in the small intestine. The enterohepatic circulation poses a problem for heavy metals detoxification because methylmercury reabsorption via this process is 95 percent efficient! Fortunately, binders can stop the vicious cycle of heavy metals recirculation by binding to metals, preventing their reabsorption and promoting their excretion via stool. Eliminating heavy metals through the intestinal tract with the help of binders prevents metals from traveling through the kidneys, which are very delicate and susceptible to damage.

Thiols, a type of sulfur-containing compound, and silica are highly effective at absorbing heavy metals and preventing their recirculation.34

For Sensitive Individuals  

Are you sensitive to numerous supplements or have a history of difficulty detoxifying? If so, your nervous system may be in “fight-or-flight” mode, preventing you from detoxifying successfully. An imbalance between sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) nervous system activity shuts down detoxification and induces hypersensitivity. If this resonates with you, you need to work on restoring nervous system balance before commencing a detox protocol. CBD and GABA have calming effects and restore balance to the nervous system, opening up detoxification pathways.

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