By Dr. Mercola
Dr. Christopher Shade, a former organic farmer, received his PhD from the University of Illinois. His education included the study of metal-ligand interaction in the environment, and for a long time, he specialized in environmental- and analytical chemistry of mercury.
About six years ago, he developed and commercialized technology for mercury speciation analysis — a process that separates and measures different forms of mercury. Shortly after starting this company, Quicksilver Scientific, he turned his focus to the clinical side, and the human body's ability to detoxify mercury.
"The heart of mercury's toxicity is what I call inappropriate binding," Dr. Shade says. "Mercury is never a free ion... [M]ercury is always bound in these covalent relationships with what's called the ligand. Mercury's favorite ligand is sulfur; specifically a reduced form of sulfur called a thiol.
This is what you have on cysteine, like N-acetyl cysteine or in glutathione [editor's note: which is why they're so important for mercury elimination]. But these thiols are all throughout your body. [M]etals... like zinc, copper, or iron... are held in place by thiol groups. Mercury has higher affinity for those thiol groups than the [other] metals do.
How much higher? For zinc — a billion times higher – 10 to the ninth. When the mercury comes by... and it sees an enzyme that's holding zinc in it, those cysteines are going to reach over and grab on to the mercury.
... Other places that mercury will bind to thiols are on cell membranes... [and] different forms of mercury will cross your blood-brain barrier."
Mercury can also displace other elements such as zinc and copper, by attaching to the receptors that would otherwise hold these essential minerals. Overall, mercury has a very strong ability to dysregulate your entire system, which is part of the reason why mercury toxicity symptoms are so difficult to pin down.
"Neurologically, it can take you into depression, or it can take you into anxiety," Dr. Shade explains. "Similarly, it can make you hyperactive, or it can give you chronic fatigue."
From a more mechanical perspective, mercury destroys the enzyme tubulin, which builds microtubules that play an important role in intracellular communication. According to Dr. Shade, you can clearly see how mercury stops the assembly of tubulin in neurological cells, causing them to fall apart instead.
The Most Common Sources of Mercury Exposure
There are two primary forms of mercury:
- Inorganic Mercury
- Methylmercury (organic mercury)
Phenylmercury was used in early paints, which is why you need to be careful with peeling paint layers in older homes. In terms of cellular toxicity, inorganic mercury rates the highest. While methylmercury penetrates your body very well, it's slightly less toxic to the cells than the inorganic form, which is what gets released from your dental amalgams. Additionally some inorganic mercury in the body is formed by breakdown of methylmercury or vaccine-based ethylmercury (another form of organic mercury). According to Dr. Shade's research, the two primary sources of mercury exposure are:
- Inorganic mercury from dental amalgam and vaccines
- Organic mercury from fish consumption
"Vaccines would come underneath that, though they're slowly removing the mercury from the vaccines. So, it depends if you get a lot of vaccines or not. Now if you're going in for flu shots routinely, you might be exposed to a fair amount of mercury," he says. "Research on spreading out doses versus punctuated doses show that punctuated or periodic high doses have more ability to penetrate the brain than distributed doses do. That's one of the worst things about getting it from vaccines."
Another source of mercury exposure comes from coal-burning power plants. This mercury pollution is distributed in the air, and is deposited in the ocean, where of course it bioaccumulates in fish. So indirectly, it's still a major source of exposure.
"The one paper that has shed some light on coal-burning was the Palmer paper coming out of Texas, where they found higher rates of autism with proximity to coal-burning power plants. But that's the only [study] that's done that," Dr. Shade says. "From all the data that I have looked at, from all the people that we have measured... fish and amalgam dominated everything. People who don't have any fish consumption and don't have any amalgam exposure, we very rarely see any significant amounts of mercury in."
Why Most Mercury Tests are Ineffective and/or Inaccurate
While I no longer see patients, when I did, one of the standard mercury tests used was a challenge test, using a chelating chemical such as intravenous DMPS or DMSA. Then you'd measure the urine for 24 hours. You can also measure the mercury content in hair and blood. However, all of these tests have drawbacks and shortfalls, and Dr. Shade has developed a testing method that far surpasses all of these earlier tests.
While most of these older tests primarily measured total mercury load (and inaccurately at that), his technology, called mercury speciation, is able to separate and measure the different forms of mercury in your system. This allows you to determine your primary source of exposure — either fish-based methylmercury, or the dental-based inorganic mercury. It can also help you evaluate how well your kidneys are processing such toxins.
Dr. Shade explains:
"When we move to speciation testing, then we're able to take something like your blood and say, 'This much of it is methylmercury from fish, and this much of it is inorganic mercury from amalgam, though some of it is from the breakdown of the fish-based mercury.'
People used to do everything as total mercury... Sometimes they couldn't really correlate that with how many dental amalgams they had. That was because blood was primarily a measure of methylmercury exposure of fish-based exposure. In the blood, you got a high representation of your fish burden, and a lower representation of your dental burden, and thus the need to separate those two. Blood was used, but blood didn't make sense for certain types of exposures. If you're exposed to elemental mercury vapor, it didn't really show correctly in the blood."
Urine analysis has similar shortcomings.
"If your kidneys are working well and you're excreting well, the amount that comes out in the urine will be linearly correlated with the amount or inorganic mercury in your blood. So as the inorganic mercury goes up from your loading, the urinary level will go up linearly. But if your kidneys are not excreting well, then the urinary output will be low, and you'll get a damming up and building up of the reservoir of inorganic mercury in your blood. You'll see high inorganic mercury in the blood, low in the urine."
So, if you're only looking for mercury in your urine, low levels of (total) mercury can be either good or bad, but you won't easily know which. A low measurement could mean you have very little inorganic mercury in your system, or it could mean your kidneys are failing to process it and the inorganic mercury is actually accumulating in your tissues. If you primarily have methylmercury from fish in your blood, it will not show in the urine.
"Urine alone is very myopic, whereas urine normalized by the amount of inorganic mercury in the blood is a very good indicator then of how well you're detoxifying or excreting that form of mercury," Dr. Shade explains.
As for hair testing, while hair is a good marker of fish-based methylmercury in your blood, it will tell you absolutely nothing about the amount of inorganic mercury you're getting from dental amalgams.
The Problem with Challenge Testing
"In a challenge test, you orally take the chelators like DMSA or DMPS. They go into your blood. They solubilize a lot of the mercury that's in your blood, and they make it able to go very easily through your kidneys. This would round up a bunch of mercury in your blood and pass it through your kidneys. Now you would get both organic and inorganic forms coming out through your kidneys.
The problem here is the same one with all urinary measurements. If you've got problems in the kidney – and this happens commonly when people are exposed for long periods of time – you might not pass that mobilized mercury out through your urine.
The other problem with the challenge test is that you don't know what the distribution is. How much of this is organic? How much of this is inorganic?
Then you got two chelators. You got DMPS and DMSA, and they're different. They bias towards one of the other form of mercury. DMPS biases towards inorganic mercury. If you have a lot of inorganic mercury exposure, you use DMPS... Then there's a mythology that the challenge test is showing you the body burden, like it's reaching into every single cell taking out a representative amount of mercury in there and taking it out of the body. That's really not true," Dr. Shade says.
So as a summary, all of the earlier testing methods offer an incomplete picture of your actual mercury load.
- Hair testing only shows organic (methyl) mercury load
- Urine testing only shows inorganic mercury load
- Blood testing for total mercury load really only gives you a measure of your mercury from fish consumption, while mercury from dental amalgams remains 'hidden'
- Challenge testing can give false low readings if your kidneys are not functioning well, and each of the chelators are biased toward one form or mercury or the other, which can give you a misleading measurement of your mercury load
Mercury Speciation — the Next Generation of Mercury Testing
Dr. Shade's mercury speciation technology overcomes all these problems by being able to separate and measure each of the different forms of mercury.
"You have got a lump sum of mercury in the sample. We want to pull them apart, so we know how much is the organic form and how much is the inorganic form," he explains. "In the environment, which is what I originally developed it for, it is very important to know this because the bulk of the environmental mercury is inorganic mercury.
Inorganic mercury – even though it's more toxic to the cell –does not accumulate well and it does not get into organisms very well, whereas methylmercury is the bioaccumulative form. That's the one that a fish swimming in the water will have a million to 10 million times more [of]... than is in the water. It's very important to be able to see the methylmercury separate from the inorganic mercury.
I developed this system where we could take a sample and relatively quickly – at least compared to the old methods – separate these two different forms... When I came to the clinical world, I started applying that... to blood and urine. What we found is that if you want to get a good measure of blood, you need to separate the methyl- and the inorganic mercury."
The ethyl- and methylmercury have different reference ranges. Methylmercury is almost always higher than the ethylmercury if you're exposed to both types. After measuring over 2,000 patients, Dr. Shade discovered that methylmercury levels in those with the highest loads is almost 15 times higher than the ethylmercury, on average.
"If you're exposed to both, the methylmercury is always going to swamp out the inorganic mercury," he says. "But once you separate those two, you can see very clearly how the two are tracking in the body. They have different targets in the body, and they have different sources coming in."
... Urine can be nicely correlated to blood inorganic mercury, as long as the kidneys are working okay. That means that as blood inorganic mercury goes up, urinary inorganic mercury should go up with it. It'll be a linear increase between the two. We can now plot out how well the kidneys are working."
Being able to chart how well your kidneys are working is a significant benefit, as this will give you a better idea of how well your natural detox system is working. If you have high levels of inorganic (ethyl) mercury in your blood, but low mercury in your urine, it's a sign that your body is retaining toxicity.
"These tend to be the sickest people and have the hardest time detoxifying," Dr. Shade says. "Then we know that we have to work more on their kidneys before we go into really moving the mercury out of the body."
The same technique is being used on hair, which, again, is an inorganic (ethyl) mercury marker. As your blood methylmercury goes up, the methylmercury in your hair should rise in a linear fashion. If they do not track together (meaning you have high levels in your blood but low levels in your hair), then it's an indication that your biochemistry has been disrupted and cannot effectively mobilize methylmercury.
On Detoxing Mercury
According to Dr. Shade, effective detoxification is highly dependent on your glutathione and sulfur metabolism. For example, when your glutathione and sulfur levels increase, you'll typically see higher levels of mercury coming out of your hair.
It's important to realize, however, that detoxing cannot be achieved overnight. Or even in a few weeks. According to Dr. Shade, most people will typically need an entire year to detox, depending on how sick you are. The sicker you are, the longer it will take, simply because you have to go slower when you're ill.
"But then you have to keep in mind one of the aspects of detoxification. You got to be mindful of that, and incorporate a lot of this into your life. I mean a lot of it is lifestyle changes that are going to keep you effectively detoxifying. Then, once or twice a year go back in for whatever period of time it takes you. Go back and do another detoxification, because even if you get all the mercury out, you're continuously exposed to all kinds of things. I mean, you've got the airborne mercury coming in. You've got little bits through the food. Then you have cadmium, arsenic, and lead coming in... you've got all the different organic toxins... pesticides and herbicides... chlorinated organics... mold-based toxins... toxins from organisms that live in your GI tract, if you don't have a perfect biotic flora...
... Probably, the biggest myth that's got to be destroyed immediately is that mercury will stay in your body until you go in there with a chemical chelator and pull it out — that mercury is never removed from the body and it just builds up forever. That is completely a myth. We'd all be dead if that were the case.
You have a system for moving mercury and other heavy metals out of your body. They may work in different efficiencies for different people, or may be totally disrupted in some, but you have a [detoxification] system."
How Your Body Detoxifies Naturally
One of the central problems in modern toxicology is the failure to fully understand the vast disparity amongst the population in their ability to deal with certain toxins, and their ability to detoxify them. We're all highly individual, and exposure levels that will cripple one person may leave another seemingly unharmed. A major part of this individual difference in tolerance is the functioning of your body's detoxification system. If your detoxification channels are working well, you will be able to withstand higher levels of toxins without experiencing obvious symptoms of toxicity.
"The core of the detoxification system is the glutathione system," Dr. Shade says. "Notice that I don't say, 'it's glutathione.' No, it's the glutathione system.
Glutathione binds to metals and can move them out of your body, but it doesn't do that alone. If we look at what the requirements for resistance to metals and effective detoxification (meaning not only the resistance but shuttling them out), you need healthy levels of glutathione in your cells. You [also] need activity of... a phase II detoxification enzyme called glutathione S-transferase. This is an enzyme that's responsible for prying the mercury off the cellular proteins and linking it together with the glutathione. [Lets say] those two parts work: You have the glutathione; you have the glutathione S-transferase — now you have a mercury-glutathione conjugate in the cell. Now you've got to get it out of your body.
At the cell membrane, you've got active transport proteins, called multidrug resistance proteins, which pushes that mercury-glutathione complex out of the cell and into your blood. From there, you got another one at the liver... [which] pulls it from your blood into your liver; and another one that dumps it from your liver into your bile tract, to go into your small intestine. You have also got some of these transport proteins in your intestinal walls, pulling [toxins] from your blood into the intestines. And you have got them in your kidneys as well.
You have to have all parts of this going."
If any one of these mechanisms is knocked out, your cells will lose their resistance to the metal, and bioaccumulation sets in. So in order to strengthen your detoxification system, you need to optimize the ENTIRE system from top to bottom within the transport chain, so that your body can pull the mercury away from the proteins it is bound to, and transport it out of your body.
Strategies for Optimizing Your Glutathione System
There are a number of different options for doing this. Taking oral or intravenous glutathione can be both expensive and ineffective. A more efficient way to optimize your glutathione levels is to provide your body with the precursor to glutathione, cysteine, in the form of foods that are naturally high in it. Whey protein, especially organic, grass-fed whey protein contains some of the highest levels of cysteine.
"Taking oral glutathione in a capsule is very inefficient, because your peptidases will break down the glutathione into its amino acids," Dr. Shade explains. "... You're left with precursors, or whey protein, which I think is probably the best precursor. Though, at the same time, you need to upregulate the activity of the synthesis enzymes that are making it from the precursors... [T]he other thing that we use a lot, which is a little bit more specialized, is liposomal delivery of glutathione.... At the same time, you're also bringing in phosphatidylcholine, which has its own therapeutic benefits by helping to repair the cell membranes. The cell membranes are very highly damaged by metals and the free radical cascades that are catalyzed by them.
We use a lot of this liposomal glutathione. We have recently taken on the manufacturing of that that's making a very small, high integrity liposome. But aside from liposomes, whey protein is my favorite way to get those precursors into the body."
According to Dr. Shade, if your body is making glutathione well, then just taking whey protein should be sufficient. But if your detoxification system is severely compromised, the liposomal glutathione can serve an important function as it can offer immediate relief against the oxidative stress caused by the mercury. He typically recommends using both for people who are ill.
"Once you have repaired the system and you're getting it working again, then the whey protein can sustain you," he says.
But it's important to remember that there's more to your glutathione system than just glutathione. You also need the proper enzymes and proteins that work together with the glutathione to eliminate the mercury. These include:
- Glutathione S-transferase
- Glutathione synthetase
- Gamma-glutamylcysteine ligase
Phylogenomics — Gene Activation through Superfoods
"This is a beautiful part of the science called phylogenomics, 'phylo' meaning plants, and 'genomics' meaning genes," he says. "What we're finding is that genes are not always [expressed]…
What are triggers to start expressing these genes?
We're finding that whole families of genes that can be upregulated together. There's protein out in the cytoplasm called the Nrf2 protein. It's held in place there by another protein called the KIP1. When certain chemical triggers hit it, it translocates into the nucleus. When it does so, a whole family of genes that have what I call the promoter region (it's a way to turn on families of genes and it's called the antioxidant response element) turns on at once. These are genes that code for production of intracellular antioxidants, as well as production of these phase II enzymes like glutathione S-transferase, and production of these phase III proteins for transport. You're helping turn up the whole system at once.
What are the things that trigger this?
Well, a lot of these things that we consider 'superfoods.' The main family of food chemicals that do this or plant chemicals are polyphenolic antioxidants like you would find in green tea extract or pine bark extract. The one we use the most is called Haritaki. We have a blend called Clear Way Cofactors, where we bring together what we think are the best polyphenolics for doing this. The other side of it is the sulfur-based chemicals."
The Importance of Sulfur Compounds for Your Detoxification System
One sulfur-based food is garlic, which has gained a reputation for being good for mercury detoxification. As explained by Dr. Shade, garlic contains sulfur molecules that trigger the translocation of the Nrf2 proteins into your cells. Thus they trigger an upregulation of your glutathione system. So it's really your glutathione system as a whole that is responsible for the chelating effect, but the sulfur compounds in the garlic upregulate that system, allowing it to do its job.
"You would want to use the whey protein in conjunction with some of these polyphenolic antioxidants, with the crucifer family, or garlic. Then you would get the enzyme up, as well as bringing in the precursors," Dr. Shade says.
As a side note, allicin is NOT the chemical responsible for upregulating the enzyme system. Allicin is part of what gives garlic its antimicrobial effect. According to Dr. Shade, taking garlic oil capsules is just as good as eating raw garlic, maybe even better, for upregulating your glutathione system. Another important sulfur compound is lipoic acid, which helps regenerate vitamin C and E.
"Vitamin C — this whole defense system that we're talking about is part of the antioxidant system," Dr. Shade says. "You need a lot of electron donors in there, feeding into the system. You're going to transfer those electrons into the glutathione. As you're using the glutathione up as an antioxidant, it's getting oxidized and needs to be reintroduced... That's the use of vitamin C: constantly bringing electrons into the system, as well as its immune effects building up the immune system. Vitamin C is an integral part of that. But you're not going to do vitamin C alone. That's a very myopic scene. But it is a strong player. It's always there. It should be one of your main pawns in this game.
Then you look at lipoic acid. Lipoic acid is a very potent upregulator of the glutathione system and specifically R-lipoate. So, without the lipoic acid, you have got two forms: You have S-lipoic acid and R-lipoic acid. These are like amino acids where you've got D amino acids and L amino acids.
L amino acid is the only one that fits into the biochemistry, and D does not. S-lipoic does not fit into the biochemistry. I mean, it can act as an antioxidant in the body. It can do some functions. But it can't upregulate the glutathione system. Only the R-lipoate fits into this Nrf2 mechanism to upregulate the glutathione system. That's why we have a liposome that's a mixture of vitamin C and R-lipoic acid. You can take high doses of this without running into bowel intolerance and very effective delivery of that lipoic acid. That's the common sulfur chemical that we use the most."
Other Helpful Players
Astaxanthin, which I've previously written about at great length, is one of the best performers when it comes to protecting your ENTIRE cell from damage, and as such, it can be an important ingredient to help optimize your detoxification system as a whole. Dr. Shade agrees, stating:
"You got the cytosol, or cytoplasm, that's water-soluble. Then you got the membranes that are fat-soluble. You need to take care of both the water side and the fat side. I think astaxanthin would be a great thing to incorporate into the systems."
Another commonly used detoxification tool is chlorella, which will help detoxify your system via your gut. Chlorella is a binder, meaning that it binds to the heavy metals present in your gut, which serves two important functions as it:
- Prevents absorption and/or re-absorption (many metals can be excreted into your bile and then be re-absorbed), and
- Prevents the metals from irritating your intestines by holding them away from the epithelia of your intestinal wall. This helps prevent inflammation
Some states, such as Colorado, are so-called "direct access" states, in which you can buy a testing kit directly from Dr. Shade's company, Quicksilver Scientific. Then all you have to do is get your blood drawn at a local lab, which sends it back to the company for analysis. In other states, you have to go through your primary care physician to get the mercury speciation test done. The test retails for about $350.
The sensitivity of the test is "unmatched," according to Dr. Shade.
"We're the only one in the world doing the speciation — the separation of the different forms of mercury. And we're the only ones working at the low ranges than we are... We have a detection limit of 10 part per trillion. Now you compare that to one of the routine labs like Lab Quest or Lab Corp; they'll do a blood mercury for you, and their detection limit will either be one or 0.5 parts per billion. That's 50 times higher, at the best, than what we're running. We're very sensitive. We run at very low levels, so we can see ALL the changes and the ambient profiles.
...I'll tell you that I like people [to be] under 0.05 nanograms per milligram for the dental form of mercury. That's when you know that you're really cleaned up. For methylmercury, that number can be a little higher. Depending upon the state of their health, I like them down below 2 nanograms per liter, or if they have shown some sensitivity to mercury, then I like them under 1 nanogram per liter."