Mercury is a pernicious neurotoxin. Removing it, however, needs to be done with great care, lest you cause even more problems.

Chris Shade, Ph.D., is probably one of the foremost experts in the world on the subject of heavy metal detoxification, and in this interview, he shares his wisdom on this important topic.

Shade received his Ph.D. from the University of Illinois Urbana-Champaign where he studied the environmental transformations of mercury.

He’s developed a patented liquid chromatographic mercury speciation technology that differentiates and identifies the exactly source of your mercury — whether it’s from your dental amalgams, or from eating contaminated seafood.

He’s also involved in developing new lipid-based delivery systems for nutraceuticals, including liposomes and micro-emulsion systems to address the need for effective and affordable detoxification.

“We had sophisticated computational tools for telling us what kind of ligands (binding molecules) are holding the mercury. What I was tasked with was developing an analytical system for separating different forms of mercury out,” he says.

“You’ve got methylmercury (which is the form that builds up in fish) and then you have inorganic mercury. In the environment, inorganic mercury is everywhere …

I developed these chromatographic tools that would enable a high-through put analysis of biological samples to separate these different forms.”

The Mercury Tri-Test

In your body, glutathione is the dominant agent that binds to and helps move mercury (and other heavy metals) out of your tissues. Part of effectively eliminating mercury involves methods that help upregulate certain aspects of your chemistry that then mobilizes and moves the mercury out.

I actually used Shade’s diagnostic tests and detox processes about five years ago to help me detox from mercury amalgams, and was able to cut my mercury level down to normal, quite quickly.

The test he developed is called the Mercury Tri-Test, because it looks at three different kinds of samples: blood, hair, and urine. You always have more mercury in your tissues than in your blood. But there’s a steady state or ratio between what’s in your blood and what’s in your tissues.

Hair is an excretion marker for methylmercury, while urine is an excretion marker for inorganic mercury. These levels should be directly proportional to the levels in your blood.

“The most telling of these, the most importantly diagnostic of these ratios, is looking at the inorganic mercury in the blood compared to the inorganic mercury in the urine.

For a given amount of inorganic [mercury] in the blood, there should be roughly a seven-fold increase in the urine, as [mercury] is filtered out in the urine. But what we find that a lot of people have low [mercury in] urine, and high [mercury in their] blood.”

What the Blood to Urine Ratios Indicate

The reason for this has to do with retention toxicity. If two people have 10 amalgams, the sicker of the two will be the one whose urine output of mercury is lower; typically due to damage to the active transport system in the proximal tubules of the nephrons.

More specifically, when the mercury in your blood rises above the 1:7 ratio to the urine, it means your proximal tubule transporters in your kidneys have been damaged.

Your kidneys filter everything in your blood. After the general filtration, in the proximal tubules your body resorbs ions and nutrients it needs to keep, while toxins are actively shuttled out into the urine flow.

“This is what we’re measuring — that movement into the urinary flow of the toxic conjugates. That area in the proximal tubules is very, very easily damaged. In mouse models, a combination of endotoxin and mercury exposure creates that damage to those transport proteins.

Obviously, probably the biggest thing on the radar of integrative and functional medicine right now is leaky gut syndrome and gastrointestinal (GI) problems. They are the number one cause of getting high endotoxin levels in your body.

If you have a high mercury level and a leaky gut, you’re very likely to damage the very transport system that’s getting that mercury out of your body.

That’s going to lead to [increased] inorganic mercury levels in the blood. That diagnostic is really important. If that ratio’s off, we need to start by treating your kidneys before we go into the main detoxification.”

The Difference Between Inorganic Mercury and Methylmercury

The Mercury Tri-Test is the only clinical test out there that differentiates between the inorganic form of mercury (typically found in amalgam fillings) and organic mercury or methylmercury (from fish), allowing you to tailor the most ideal detoxification protocol for your situation.

While many believe all mercury is the same, this is not necessarily the case. Inorganic mercury is much more toxic to the extracellular matrix and thus to connective tissues.

If you’re having joint problems or fibromyalgia-like pain, you need to work on getting rid of this inorganic mercury, and you need to make sure your kidney transporters are working well.

Metylmercury is a less cytotoxic (toxic to the cells) form of mercury. If you only have methylmercury in your body, it’s all going through glutathione conjugation to your liver, and on to your GI tract.

On the cellular level, the inorganic mercury, is more disruptive because it can bind to more sulfhydryl groups and disrupt more chemistry than methylmercury can.

“For instance, if somebody only has methyl mercury exposure from eating fish and has no amalgams … they’re going to break down a certain amount of the methyl mercury into the inorganic mercury pool. But that’s not a fixed rate. That’s an individual reaction that we don’t really understand.

I suspect it’s related to oxidative stress. But some people break down a lot and really build up this inorganic mercury pool despite not having amalgams; some people breakdown only a little bit.

Those who break down a lot are much more at risk from toxicity from their fish than if they’re not doing that. They have two forms of mercury building up in their blood, including the worst one — the inorganic mercury. It’s important that we divide those and see how well you’re excreting the two.”

Primary Sources of Mercury Exposure

Seafood is essentially the sole source of methylmercury. However, it’s a major source of mercury, and it can be problematic if you eat a lot of seafood. The type of seafood you eat also plays a big role. At the top of the food chain, a shark might have 4 parts per million (ppm) to 10 ppm methylmercury in its tissues. According to Shade, swordfish is routinely 1 to 5 ppm, and tuna is routinely in the 1 to 2 ppm range

Toward the bottom of the food chain you have sardines and anchovies, which may contain 1 to 10 parts per billion (ppb) of methylmercury, or nearly 1,000 times less mercury.

Wild salmon like Coho and sockeye can be in the 10 to 100 ppb range — a hundred-plus-fold lower level than high-level shark, tuna, and swordfish. Depending on the fish you compare, there could be a thousand-fold difference between the mercury levels. To put that into perspective, it’s like eating 1,000 pounds of anchovies versus 1 pound of shark. So if you eat fish on a regular basis, it’s really important to look for species known to be low in mercury.

“A dentist I know, Dr. Dave Regiani, had mercury levels measured with us. I said, ‘You obviously don’t eat any fish. He goes, ‘I eat fish every day.’ So I said, ‘Sardines and anchovies?’ He said, ‘You got it.’ It looks like he’s not eating fish at all. When you get down into kippers, anchovies, and sardines, you can eat them at will all day long, and you’re never going to build up high levels [of mercury].”

Inorganic mercury exposure is dominantly from dental amalgam and the breakdown of fish-based mercury into the inorganic form. Airborne mercury is the third and least troublesome source. Exceptions include some older buildings, such as old medical, dental, agricultural, and scientific buildings, where mercury levels could be quite significant.

How Mercury Damages Your Health

Inorganic mercury and cadmium are the two heavy metals that cause the most damage to your kidneys. They tend to build up there, causing a downward spiral where the more damage there is to the proximal tubules, the more metals accumulate, and the more damage is created. Many have suffered damage from doing chelation for this reason. By using the Tri-Test, you can determine whether chelation is a good idea or not.

When you take a chelating agent, such as DMSA, you solubilize a lot of mercury in the form that needs to be filtered out through the proximal tubules. This can be a risky type of mercury detoxification and typically isn’t necessary. Nevertheless, if you choose to use it, make sure you are working with a highly skilled clinician in this area.

This is because if your kidneys are not working properly, then mercury gets bound up, causing inflammatory damage around the kidneys, which can actually worsen the problem by causing chronic renal insufficiency. (On a side note, a relatively low-protein diet [typically less than 40 to 50 grams per day] can be a beneficial strategy if you have kidney problems such as this.)

“The central nervous system and nephrotoxicity (or kidney toxicity) are the most well-understood damages,” Shade says. “It should be said that in neurotoxicity, the most common site for damage is the N-methyl-D-aspartate (NMDA) receptor or the glutamate receptor, which causes hyperglutamate activity, which leads to anxiety.

Glutamate excess or excess activity of the glutamate receptor makes a chronic peroxynitrite free radical cascade coming off of those receptors that causes neuroinflammation, which gives you brain fog and fuzzy thinking. It also causes a lot of anxiety and disrupts your autonomic nervous system function … That’s another downward spiral.

Thyroid problems is also a huge one — hypothyroid activity or lack of thyroid activity. It’s mostly damaging the deiodinase, which takes the T4 and moves it to T3. If you’re looking at your thyroid labs and you have a high T4 but a low T3, mercury, cadmium, or arsenic are the most dominant players in breaking that chain.

Inorganic mercury also builds up in connective tissue, leading to a lot of joint pains. If you’re having lower back pain, a lot of hip pains, connective tissue pains, or diffused pains like fibromyalgia, and you have dental amalgams, that’s a very common situation. We see people’s joint pains and connective tissue pains clear up a lot when they get rid of their amalgams and clear all that mercury out.”

The Importance of Optimizing Your GI Tract

Fortunately, there are solutions to these problems, and Shade’s work has led to treatment strategies that are far safer and more effective than earlier detox methods used by many alternative practitioners, including myself and Shade.

“Most of us are pioneers because we poison ourselves and had to figure ourselves how to get out of that. That was exactly what I did and that’s exactly how this all came about …

Nigel Plummer, Ph.D., (one of the probiotic leaders of the world) and Dr. Robert Rountree (one of the leaders in GI and functional medicine) were speaking back to back at the Colorado Functional Medicine Forum, talking about how the GI tract reacts to the toxins coming through it and is signaling your immune systems on how to do things.

At the time, I was doing really badly with my DMSA chelation protocol, and I suddenly realized I was accumulating mercury in the GI tract and not moving that out. That was stagnating the system. I started taking strong mercury binders. We have one called Intestinal Metal Detox (IMD), which is a silica particle saturated with sulfhydryl groups. One 6-gram bottle of that is equal to 3,000 to 5,000 chlorellas, which is what had been used naturopathically.

Once I cleared that metal out of the GI tract, it seemed to open up the liver’s ability to work with the small intestine, start moving that load out of there, and take the load away from the kidney. It worked so well, that provoked me to do a lot of research and figure out exactly why it worked,” Shade says.

In short, when there’s inflammation and/or toxin build-up in the GI tract, the movement of toxins from the liver and the GI tract ceases, and everything gets shuttled over to the kidneys. Unless you can open up that liver-GI path, you end up overloading your kidney with toxins. Then, if you try to mobilize all that mercury with a chelator, it all hits the kidneys and cause even more damage. So part of the solution is to “clear out” the GI path first.

Detox Step 1: Optimize Your Filtration Mechanisms

Intestinal Metal Detox (IMD) is a powerful mercury and heavy metal chelator, hundreds of times more potent than chlorella. It helps take the pressure off your kidneys by restoring the natural dominant detox pathway — from your liver to your GI tract and out through fecal excretion. So the first part of the detox involves clearing the metal out of your GI tract with specific metal binders.

The primary endotoxin binder is charcoal, and clay binds to aflatoxin. Ideally, you’ll want to use a combination of IMD/chlorella, charcoal, and clay to cover all the bases. Quicksilver Scientific is the sole source for IMD. Chlorella, charcoal and clay can be found in most health food stores and grocery stores.

“I like a cocktail of GI binders, including a metal-specific one like IMD or chlorella, charcoal (which gets almost all the other mycotoxins, except for aflatoxin), and clay (which gets aflatoxin but not the other mycotoxins). Then you’ve got the pesticides and herbicides. In that mix of different binders, you’re going to be able to get almost all of them. It’s really important in a detox to have a good cocktail of GI binders,” Shade says.

Remember, detoxing involves moving the toxin out of the cell; squeezing the toxin out of the cell into your blood circulation, and then filtering out the metals through your kidneys, liver, and GI tract. However, you need to begin by assessing your filtration capacity beforeyou start moving toxins out of your tissues. If you’re feeling awful, it means toxins are building up in circulation faster than they’re being filtered out.

To ensure your filters are working properly, begin by supporting your kidneys, liver, and GI tract, and use binders to capture and eliminate metals and toxins in your GI tract.

Classic herbs known to support healthy liver and kidney function include: dandelion, milk thistle, and bitters like gentian and myrrh. For added kidney support, cranberry (a diuretic), solidago (goldenrod), and corn silk can be used. Shade’s favorite is goldenrod. General kidney and liver support formulas are also viable options.

Adding burdock will help clear your blood. Dandelion is a good all-around option as it supports blood, liver, and kidney. Be sure to drink lots of water to flush the toxins out.

Detox Step 2: Address Detoxification Biochemistry

Next, you need to optimize the metabolic biochemistry needed for detoxification. That biochemistry involves glutathione and the enzymes and transporters that work with it, such as the enzyme glutathione S-transferase (GST), which is responsible for catalyzing and moving the mercury off the cellular proteins onto the glutathione.

There are several well-known nutraceuticals that help accomplish this. The most well-known and most reliable is lipoic acid. R-lipoic acid is the biologically active form, which is the most useful. Alpha-lipoic acid does work, but that’s a mixture of R-lipoic acid and S-lipoic acid, the latter of which actually works against the process. So R-lipoic acid (sometimes also called R-alpha-lipoic acid) is the one to look for.

“R-lipoic acid hits a switch called nuclear factor erythroid 2 (Nrf2). It’s a protein made to translocate into the nucleus. It hits promoter regions on genes. Promoter regions are signals for families of genes to turn on. If you want to accomplish something, there’s usually not just one protein that does it; there’s a family of proteins.

A promoter regions brings up a family of proteins. The Nrf2 promoter region is called the antioxidant response element. It brings up the family of detox or chemo-protection genes.

There are a number of different nutraceuticals and also pro-oxidants that do that … My favorite is called haritaki or terminalia chebula. It’s an Ayurvedic plant filled with polyphenols … Then you’ve got sulfur compounds from brassicas. Sulforaphane is a well-known one from broccoli seed extract. Erucin comes from all the brassicas.

You’ve got allicin and diallyl disulfide from garlic. All of these upregulate Nrf2. They create little free radical cascades that hit that Nrf2 and move it into the nucleus, so that you can detoxify the compounds. So in effect, these compounds are well targeted mild toxins that stimulate a response from the body.”

Which Is Best? Precursors or Direct Delivery or Glutathione?

If everything is working well in your body, you can simply use precursors to glutathione, like N-acetylcysteine (NAC) which will support glutathione production. If things aren’t working well, Shade recommends using a direct delivery of glutathione.

It’s important to realize that most oral glutathione supplements do not work. It’s simply going to break down to its constituent amino acids, so it’s not an effective intervention. Shade recommends and uses a nanoliposomal glutathione that absorbs under your tongue and is far easier and less expensive than IV glutathione.

Again, whether you can make do with precursors or need direct delivery of glutathione has a lot to do with how well your glutathione system is working, and your current state of health. Poor immune function is a sign of glutathione insufficiency, and a tip-off that a precursor might not be enough. In studies on HIV positive patients, 1,000 times more precursor than glutathione was necessary to restore cellular function in those with active disease.

“Another example of that is the herpes family. Cell cultures of herpes 1, the herpes that you get on your lip, will grow in a petri dish and kill all the cells. If you put glutathione in first, it doesn’t grow at all. If you start it and it starts killing the cells, and you throw glutathione in it, it stops it in its tracks. In fact, liposomes are a topical as well as a systemic. They were originally used in the cosmetic industry.

You can use a liposomal glutathione topically to penetrate in and help stop the propagation of a virus in a cold sore or any other herpes diseases,” Shade says. “You hear reports from people who get their amalgams out, detoxify and bring their glutathione system up that they stop getting recurring herpes infections, because herpes is living in the situation of reduced glutathione in the immune system.”

Leave Chelation for Last

The chelating agent EDTA is a powerful biofilm breaker. When taken systemically it opens up biofilms throughout your body, revealing various organisms to your immune system. As a result, you may experience immune reactions. A lot of the fatigue that people feel when chelating is in fact due to immune reactions to organisms, and is reflective of systemic biofilm-based infections. According to Shade, “If you’re not having success with detox, you need to go after microbial injections almost every time.”

Also, it’s important not to indiscriminately chelate for lead. If you go through the glutathione system upregulation discussed above, you’re not just getting mercury, cadmium, and arsenic out. You’re also getting a whole host of other toxins, including fluorinated, brominated, chlorinated hydrocarbons, pesticides, and herbicides.

“Start low, work up, and pulse on and off. That’s the key to making that happen. That will stop the toxic manifestations of lead. But mobilizing lead out of the body using EDTA, DMSA, or 2,3-Dimercapto-1-propanesulfonic acid (DMPS) has to be done with a qualified practitioner.

I would say, do the glutathione system upregulation. Get rid of all that other junk. Really build up your body’s own ability to deal with these toxins, and then mobilize the lead. And always do that with a practitioner,” Shade says.

Addressing Toxic Metals Besides Mercury

To detect heavy metals besides mercury, Shade uses an inductively coupled plasma mass spectrometry (ICP-MS) scan of blood for nutrient and toxic metals. This is important, because you need to have your nutrient metals in order before you can go after toxic metals. Most of the toxic metals displace zinc, and zinc drives many important metabolic reactions. If you have low zinc, you’re not going to be able to detoxify metals well.

If you have high copper and low zinc, you will present symptoms of heavy metal poisoning, and it will be synergistically toxic with any heavy metals present in your system. High calcium and low magnesium stops detoxification by restricting magnesium-dependent transporters and by putting you in a state of chronic inflammation. You also need to have adequate molybdenum, selenium, and lithium in order to detoxify.

“You need to bring up the ones that are low, and you need to stop supplementing or stop exposing yourself to the ones that are high. It’s a little bit more complex with copper. But generally, when you get the glutathione system in order and when you get methylation in order, the copper levels will come down.

Now as far as the toxic metals, when we do glutathione system upregulation, we handle mercury, cadmium, and arsenic — three of the Big Four. The only one we really want to chelate for is lead. If lead is very high, you need the guidance of a qualified licensed practitioner to use either our liposomal EDTA or a little bit of DMSA and DMPS.

In general, I don’t like DMSA and DMPS unless you’ve already cleared the system of the mercury, you’ve normalized the glutathione system, and you’ve established very importantly that your kidneys are able to filter those chelates.”

Three Pillars of Detoxification

The three pillars of detoxification in general and metal detoxification in particular are:

1. Cleanse and clear your GI tract of metals and toxins using a thiol-functionalized silica (Intestinal Metal Detox, or IMD) with a practitioner, or chlorella, plus charcoal and clay, which bind to all the other toxins. Herbs like dandelion and goldenrod are good for added liver and kidney support. Burdock and dandelion helps clear your blood. Be sure to drink extra water to flush the toxins out.

Remember, if you’re detoxing and feeling really unwell, you need to clear more toxins out of your GI tract and blood. When you do that, back off your Nrf2 upregulators, and instead take more GI binders, and more liver and kidney supporting herbs. Drink a lot of water. When you’re feeling clear again, restart the Nrf2 upregulators.

2. Glutathione optimization. Increase glutathione levels either by using precursors (such as N-acetylcysteine [NAC], or a liposomal glutathione formulation.

3. Nrf2 upregulation in the cells using R-lipoic acid, polyphenols, and sulfur-based compounds from cruciferous vegetables and alliums. The Ayurvedic herb haritaki is beneficial, as are sulforaphane (broccoli seed extract), and allicin and diallyl disulfide (garlic). All of these upregulate Nrf2 and aids detoxification.

Last but not least, remember that detoxing is a marathon, not a sprint. Start all your doses low and work your way up. Do not jump in and do too much all at once. Typically, detoxing will take anywhere from three to 12 months; sometimes longer. Also, pulse the treatment on and off, or else it will lose its effectiveness.

“You have to do it and then let it come down. Stimulate. Relax. Stimulate. Relax. We start with five days on, two days off. If that’s a little heavy for you, four days on, three days off. Once we get a little deeper into it, we move it up to 10 days on, four days off.

A study regarding that: when they looked at upregulation of these genes using phytochemicals (plant-based chemicals) in mice, they saw that when they gave them a high dose, they went up to a max expression in 10 days. That was three-fold their baseline.

On the same dose, over the next 20 days, going up to 30 days, the expression went down, down, down, until it was back at baseline. Meaning, when you use these compounds that upregulate every day, they stop working for you. You’ve got to take them; then stop. Take them. Stop.”