In Parts One and Two of our Back to Basics blog series, we discussed heavy metals toxicity and testing. In this third and final installment in the series, we’ll cover how to safely and effectively detoxify heavy metals from your body so that you can get one step closer to optimal health!
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. Quicksilver Scientific offers the only therapeutic detoxification protocols that address all three phases of detox. When you use a Quicksilver Scientific detox kit, you can rest assured knowing that the protocol you’re using is both safe and effective.
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.
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.
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
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 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
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
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 IMD contains purified silica with thiol groups attached to assist with heavy metal burden. Additional helpful binders include charcoal, which is adept at removing endotoxin, clay, zeolite, chitosan, acacia gum, and aloe.
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.
Are you feeling overwhelmed about detoxification? Our Deluxe Detox Qube and Detox Qube with EDTA make the process simple by combining all the necessary elements for heavy metals detoxification in one convenient kit. Our Deluxe Detox Qube is our most comprehensive protocol, offering glutathione, liver, nervous system, and mineralization support. The Detox Qube with EDTA provides all the factors for heavy metals detox, with optional add-on support for the adrenals, kidneys, liver, and gallbladder, and nervous system.
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- Murray M, Zhou F. Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease. Br J Pharmacol. 2017; 174(13): 1908-1924.
- Pall ML, Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao. 2015. 67(1): 1-18.
- Unoki T, et al. Molecular pathways associated with methylmercury-induced Nrf2 modulation. Front Genet. 2018; 9: 373.
- Jan AT, et al. Heavy metals and human health: Mechanistic insight into toxicity and counter defense system of antioxidants. Int J Mol Sci. 2015; 16(12): 29592-29630.
- Ganey PE, Roth RA. Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents. Toxicology. 2001; 169(3): 195-208.
- Rumbeiha WK, et al. Augmentation of mercury-induced nephrotoxicity by endotoxin in the mouse. Toxicology. 2000; 151(1-3): 103-116.
- Fan K, et al. Lipopolysaccharide-induced dephosphorylation of AMPK-activated protein kinase potentiates inflammatory injury via repression of ULK1-dependent autophagy. Front Immunol. 2018; 9: 1464.
- Purohit V, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences. Alcohol. 2008; 42(5): 349-361.
- Bjarnason I, Takeuchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. J Gastroenterol. 2009; 44(Suppl 19): 23-29.
- Goshal UC, et al. Small intestinal bacterial overgrowth and irritable bowel syndrome: A bridge between functional organic dichotomy. Gut Liver. 2017; 11(2): 196-208.
- Allain T, et al. Interactions of Giardia sp. with the intestinal barrier: Epithelium, mucus, and microbiota. Tissue Barriers. 2017; 5(1): e1274354.
- Hollon J, et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015; 7(3): 1565-1576.
- Rodino-Janeiro BK, et al. Role of corticotropin-releasing factor in gastrointestinal permeability. J Neurogastroenterol Motil. 2015; 21(1): 33-50.
- Costa RJS, et al. Systematic review: exercise‐induced gastrointestinal syndrome—implications for health and intestinal disease. Aliment Pharmacol Ther. 2017; 46(3): 246-265.
- Vasiluk L, Pinto LJ, Moore MM. Oral bioavailability of glyphosate: studies using two intestinal cell lines. Environ Toxicol Chem. 2005; 24(1): 153-160.
- Bernhoft RA. Mercury toxicity and treatment: A review of the literature. J Environ Public Health. 2012: 2012: 460508.
- Zeevalk GD, et al. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010; 35(10): 1575-1587.
- Inokuchi A, et al. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J Biol Chem. 2001; 276(50): 46822-46829.
- Crocenzi FA, et al. Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochem Pharmacol. 2005; 69(7): 1113-1120.
- Tang X, et al. Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice. J Ethnopharmacol. 2016; 194: 63-71.
- Cui J, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem. 2003; 278(12): 10214-10220.
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- Houghton CA, et al. Sulforaphane and other nutrigenomic Nrf2 activators: Can the clinician’s expectation be matched by the reality? Oxid Med Cell Longev. 2016; 2016: 7857186.
- Sun X, et al. AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression. Cell Death Diff. 2017; 24(5): 819-831.
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- Liu JF, et al. Reduction of lipid accumulation in HepG2 Cells by luteolin is associated with activation of AMPK and Mitigation of oxidative stress. Phytother Res. 2011; 25(4): 588-596.
- Shen QW, et al. Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha-lipoic acid in C2C12 myotubes. Am J Physiol Cell Physiol. 2007; 293(4): C1395-C1403.
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- Weng Z, et al. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J Allerg Clin Immunol. 2015; 135(4): 1044-1052.
- Wang TTY, et al. Elucidating the role of CD84 and AHR in modulation of LPS-induced cytokines production by cruciferous vegetable-derived compounds indole-3-carbinol and 3,3′-diindolylmethane. Int J Mol Sci. 2018; 19(12): 339.
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