Heavy metals have been shown to bind proteins and prevent their functioning and to disrupt cellular function by interfering with necessary minerals like zinc and magnesium and causing oxidative stress [R].
Symptoms of heavy metal intoxication include:
Studies in worms have shown that these metals have synergistic toxicity, meaning that combined they are more toxic than the sum of their toxicities together [R].
The vast majority of research on heavy metal and chelation therapy focuses on these 4 metals as they are present in disproportionately higher levels in the environment than other heavy metals and have the greatest likelihood to produce health issues [R].
This article will focus on how to safely and effectively remove the “Big Four” heavy metals: lead, arsenic, mercury, and cadmium.
Types of Toxic Heavy Metals and Why They’re Bad
Mercury is considered to be the most toxic heavy metal in the environment [R].
The majority of exposure to mercury is due to seafood, with additional sources including occupational exposure such as small-scale gold mining and dental amalgam installation and removal [R].
Mercury accumulates in organisms as you go up the food chain, meaning larger fish such as tuna, shark, and swordfish have proportionally more mercury than smaller fish like sardines, mackerel, and anchovies [R].
Because it’s attracted to fat (lipophilic), the metal accumulates in the fat and liver of fish, and when consumed by humans it accrues in the brain and nerves (specifically the myelin sheaths of nerves, which are made of fats) [R]. The brain, kidneys, and liver are the major storage sites for mercury accumulation.
Mercury poisoning can cause:
Chronic mercury exposure is associated with:
Higher mercury levels were found in the brain and blood of Alzheimer’s patients. In animals, low levels of mercury are able to cause cell deterioration similar to what is seen in Alzheimer’s disease [R].
Moreover, mercury levels range from 2-10 times higher in individuals with dental amalgams, and women with dental amalgams had a 13% increased risk for Alzheimer’s disease compared to women without them [R, R].
Mechanism of Harm by Mercury
Mercury increases the formation of reactive oxygen species, both directly by being a pro-oxidant and indirectly by depleting crucial antioxidants like glutathione, which leads to an increase in oxidative damage to DNA, lipids, and proteins [R].
Mercury can also bind to key amino acids and enzymes like glutathione, cysteine, and sodium-potassium adenosine triphosphatase. This binding disrupts cellular function [R, R].
The neurotoxic effects of mercury are likely due to its ability to increase levels of glutamate. Excess glutamate levels damage neurons leading to neuronal death [R, R].
Chronic exposure to arsenic causes a variety of symptoms and health conditions.
Foods grown in contaminated soil and water are the main sources of intake for most people [R].
Also, people working in glass-making, smelting, pesticide manufacturing, and semiconductor manufacturing industries may be exposed to significantly higher levels of arsenic than the general population [R].
In recent years, there were scandals where high levels of arsenic were found in rice and apple juice. It’s recommended that babies don’t drink rice-based drinks because of this [R, R].
The primary targets for arsenic and compounds containing arsenic are the kidneys and the liver because they are generally processed by the liver and excreted in the urine [R, R].
Excessive exposure during childhood can lead to behavioral dysfunction during puberty even lasting into adulthood [R].
Arsenic exposure has also been associated with:
- Deficits in verbal intelligence long-term memory in children [R]
- Diabetes [R]
- Increased fetal mortality and preterm birth [R]
Long-term exposure can cause:
- Inflammation of the nerves, causing pain and loss of function [R]
- Skin lesions, darkening of the skin (hyperpigmentation) [R]
- Internal cancers including bladder, kidney, liver prostate, and lung [R]
- High blood pressure [R]
- Increased risk of mortality [R]
- Toxic effects on genes, which can cause mutations [R]
Mechanism of Harm by Arsenic
Arsenic exerts its toxic effect by inhibiting enzymes in the mitochondria, replacing phosphorus in various biochemical reactions, depleting thiamine(vitamin B1), and causing oxidative stress through depletion of key enzymes like glutathione and superoxide dismutase (SOD) [R].
Up until recent years, lead was often used in paints, ceramics, and pipes. Although its use in these products has been significantly reduced, a report found that 25% of homes in the US have significant amounts of lead-contaminated paint, dust, or soil [R].
The majority of lead poisoning cases in adults are due to occupational exposure, such as inhaling lead-contaminated dust, while lead exposure in the general population is mainly through food [R].
Lead can accumulate in the kidneys, liver, heart, brain, and especially in the bones [R].
Symptoms of lead exposure on the brain include:
- Headaches [R]
- Poor attention span [R]
- Irritability [R]
- Memory Loss [R]
Lead exposure is of particular concern in pregnant women, as it easily crosses the placental barrier and enters the developing fetus. Both human and animal studies show that lead exposure during pregnancy is associated with reduced birth weight and preterm delivery, as well as cognitive deficits in the offspring [R, R, R].
Mechanism of Harm by Lead
The main mechanism by which lead exerts toxic effects is through its ability block the actions of calcium and disrupting the activity of various enzymes and proteins, including glutathione and superoxide dismutase, and causing oxidative stress [R].
Cadmium is a relatively highly water-soluble metal. In smokers, tobacco is the main source of cadmium because tobacco plants tend to accumulate the metal from the soil [R].
For non-smokers, the main source is through diet and occupational exposure, including metal industries, soldering, battery manufacturing, and cadmium-contaminated workplaces [R].
Cadmium is highly toxic to the kidneys and preferentially accumulates in a specific type of cell (proximal tubular cells) [R].
Long-term exposure can cause:
- Kidney disease [R]
- Osteoporosis [R]
- Disrupted calcium metabolism [R]
- Kidney stones [R]
Mechanism of Harm by Cadmium
Although the mechanisms of cadmium toxicity are not fully understood, research suggests it causes oxidative damage indirectly by decreasing antioxidants, rather than directly creating free radicals like the other metals discussed [R].
Cadmium also tends to bind to key enzymes and proteins, preventing them from functioning normally [R].
Due to its damaging effects on the kidney, cadmium toxicity tends to disrupt calcium balance, which the kidney plays a large role in regulating [R].
How to Test for Heavy Metals
Physicians often test for heavy metals using urine, whole blood, red blood cell, and less commonly, hair, or rarely, toenail samples [R].
Blood Tests for Heavy Metals
In most cases blood testing is indicative of acute exposure rather than the total body burden (total amount of heavy metals accrued over one’s lifetime that is present in the body), however, there are exceptions [R].
Urine Testing for Heavy Metals
Urine testing is the gold standard for the “Big Four” toxic metals (mercury, arsenic, lead, and cadmium). However, even urine test can give an inaccurate representation of body burden for some metals, as they are often present in different forms, stored in different areas and processed by and excreted by the body differently [R].
For example, mercury is present in the body in two forms: organic (methylmercury or dimethylmercury) and inorganic (mercury salts, such as mercury chloride). Organic is largely excreted through the bile and feces, while inorganic is eliminated via the urine [R].
Therefore, whole blood is the preferred test for organic mercury body burden and urine testing is optimal for a measure of the body burden of inorganic mercury [R].
The Heavy Metals Challenge Test
A popular type of test is called the “challenge test”, or “provoked urine test,” which involves using large doses of a strong chelating agent, usually dimercaptosuccinic acid (DMSA), to draw metals out of the body and into the urine where they can be analyzed [R].
Chelation the process by which the body naturally binds toxic heavy metals in order to prevent them from causing harm and to excrete them from the body [R].
Chelation challenge tests are associated with adverse reactions, as the influx of mobilized metals can oftentimes overwhelm the body’s detoxificationpathways as well as redistribute them to different or more critical tissues during the test [R].
Other criticisms of challenge testing include the possibility of false positives and lack of a standard of protocol and laboratory reference ranges to interpret the results [R, R].
Therefore, many professional and government organizations strongly recommend against their use because of this [R].
Despite this, the test is still commonly used by some practitioners. These clinicians argue that it allows them to determine the most effective chelating agent and to detect an absorption or tolerance problems with the agent [R].
If an individual decides to go the route of the challenge test, it is advised that their excretory pathways are open and not overburdened, i.e. in conditions like constipation or kidney and liver diseases, so as to allow the metals to pass out safely [R].
Additionally, urine samples should be taken pre- and post-challenge testing to establish a reference for the individual [R].
Instead of challenge testing, heavy metal toxicity is often diagnosed with a combination of reported symptoms and urine tests that reveal metal levels above the reference range [R].
Hair Testing for Heavy Metals
If done correctly, hair analysis is another reliable way to see if you have heavy metal toxicity [R]. Hair testing mainly reflects past exposure, so it should be combined with urine or blood testing to confirm heavy metal toxicity [R, R].
How to Safely Chelate and Detoxify Heavy Metals
The overall goal in chelating and detoxifying heavy metals is to bind them with a strong chelator and then excrete them safely out of the body without redistributing them to other organs.
1) Supplement with Essential Minerals
During this process, supplementation with zinc, calcium, iron, and magnesiumis recommended, as these nutrients reduce the absorption of toxic heavy metals and their depletion results in enhanced toxic metal uptake from the gut [R, R, R, R].
2) Remove Sources of Heavy Metal Exposure
The first step in reducing the body burden of heavy metals is to reduce or remove the source of exposure, if possible. This may mean reducing consumption of high mercury seafood, testing and filtering drinking water, or quitting smoking.
3) Ensure that Excretory Organs Function Correctly
If you will use chelation to remove toxic heavy metals, it is important to ensure that your excretory pathways are open and not overburdened in order to allow the metals to pass out safely. Constipation, leaky gut, or kidney and liver diseases will prevent metals [R].
4) Bind (Chelate) Heavy Metals
The next step is to bind heavy metals where they are stored in the body, escort them into the bloodstream, and excrete them through the liver via bile in the feces, through the kidneys via urine, or through the skin via sweat [R].
5) Detoxify Slowly or Pulse the Chelation Process
It is important to detoxify from heavy metals slowly to prevent redistribution through the body and therefore it is recommended to temporarily discontinue or lower dosages of chelating compounds if symptoms worsen and allow the body’s detoxification and excretory systems to “catch up” [R].
Moreover, it is generally advised to pulse the chelation process and to work with a qualified physician during this time.
Supplements that Help with Heavy Metal Chelation and Detoxification
1) Glutathione Protects Against Mercury Toxicity
Glutathione is a powerful antioxidant that is produced from three amino acids: cysteine, glutamic acid (closely related, but not to be confused with glutamine), and glycine.
Glutathione contains sulfur components that readily bind with mercury, lead, and cadmium [R].
Other compounds that have thiol groups include the amino acid cysteine, albumin, and metallothioneins. Mercury has a high affinity for thiol groups and will readily bind to the thiol-containing compound (usually glutathione) in the highest concentration [R].
Higher levels of glutathione protect against mercury accumulation [R].
Mercury has been shown to deplete glutathione levels in brain cells, red blood cells, and kidneys [R, R, R].
Glutathione protects against mercury in 4 ways:
- Binding to it and preventing it from causing damage to enzymes and cells [R]
- Preventing the mercury from entering the cell where it does the most damage [R]
- Helping transport and eliminate it from the body [R]. Indeed, glutathione mercury complexes are the most abundant form of mercury in both bile and urine [R].
- Serving as an antioxidant that neutralizes the free radicals such as hydrogen peroxide and lipid peroxides that are produced by mercury [R].
You can learn how to increase your glutathione levels in this post.
2) Alpha-Lipoic Acid Protects Against Arsenic, Cadmium, and Mercury Toxicity
Alpha-lipoic acid (ALA) is another strong antioxidant with the ability to penetrate the cell membrane as well as cross the blood-brain barrier to chelate heavy metals stored there [R, R].
This is important as lead and mercury easily accumulate in the brain [R, R].
Alpha-lipoic acid decreases damage to cell membranes (lipid peroxidation), which can be caused by heavy metals [R].
Alpha-lipoic acid has also been shown to increase glutathione levels both inside and outside of the cell by regenerating used glutathione to make it active again [R, R].
Additionally, alpha-lipoic acid increases the production of glutathione by increasing the uptake of cysteine, the rate-limiting component of glutathione, into the cell [R].
Although no clinical trials have investigated the use of alpha-lipoic acid in chelating heavy metals, animal studies show that the compound reduces uptake of cadmium into liver cells and prevents absorption of arsenic in the intestines [R, R]
Of note, animal studies have also shown that alpha-lipoic acid has the potential to redistribute heavy metals, however, these studies have administered the compound intravenously, which may cause alpha-lipoic acid to combine with glutathione in the liver and prevent the glutathione from carrying heavy metals out of the body [R].
This effect has not been seen in human trials with alpha-lipoic acid and the vast amount of evidence strongly suggest that it can prevent the damage caused by heavy metals as well as help glutathione bind to and excrete metals [R, R, ].
Oral doses of as much as 1,800 mg/day of alpha-lipoic acid are well-tolerated with no side effects in clinical trials [R].
3) Modified Citrus Pectin Increases Lead, Cadmium, and Arsenic Excretion
Pectin is a fiber in plants. Modified citrus pectin (MCP) is a form of pectin that has been altered to be more digestible.
In children with high blood levels of lead, 15 grams of MCP a day for 28 days decreased lead in the blood, while urine lead levels increased by more than 132% (indicating lead removal) [R]. No side effects were reported.
Another study found that 15 grams of modified citrus pectin a day for five days increased urinary excretion of arsenic (130%), cadmium (150%), and lead (560%) [R].
Note: the studies were performed by the creator of MCP.
4) Sauna/Sweating Increases Arsenic, Cadmium, Lead, and Mercury Excretion
Sauna use increases the circulation throughout the skin and induces sweating, with blood flow to the skin increasing from 5-10% of the amount of the blood pumped through the heart at rest to 60-70% [R].
Sweating, caused by either exercise or sauna use, has been shown in many studies to excrete clinically meaningful levels of arsenic, cadmium, lead, and mercury, in some cases surpassing the amount excreted in urine [R, R, R, R].
Beneficial metals, vitamins, and electrolytes, such as zinc, copper, manganese, vitamin E, sodium, and chloride, are also lost during sweating. Therefore, it is crucial to consume a diet sufficient in these nutrients to counteract any loss due to sweating.
5) Vitamin C Protects Against Lead Toxicity
Low vitamin C levels have been associated with decreased glutathione levels and increased oxidative stress [R].
Vitamin C increases glutathione levels by recycling used glutathione, as in human red blood cells (DB-RCT) [R].
In rats, vitamin C supplementation increases lead excretion in the urine and feces and prevent lead absorption in the intestine [R].
Lead toxicity can lead to damage to the membranes of red blood cells, impairing their function. In 15 workers exposed to lead, one year of vitamin C (1 g/day) and E supplementation (400 IU/day) reduced lipid peroxidation in red blood cells between 47.1% and 69.4%, comparable to 19 non-lead exposed workers [R].
Dosages between 500-1500 grams a day are often used in clinical research settings, however many users greatly exceed these levels, with few adverse effects beyond diarrhea.
6) Selenium Increases Mercury Excretion
Selenium is a crucial nutrient when it comes to chelating heavy metals.
The mineral increases the activity of glutathione, and increased levels of selenium are associated with increased levels of glutathione in the blood [R, R].
In rats exposed to mercury, selenium prevented the destruction of neurons and suppression of protein synthesis caused by mercury and helped repair damaged tissue that helps conduct nerve signals (myelin sheath) [R].
In 103 mercury-exposed villagers in China, 100 micrograms of selenium daily in the form of enriched yeast increased mercury excretion and as well decreased markers of inflammation and oxidative stress compared to controls who were given the yeast without selenium [R].
Brazil nuts are often mentioned as important food to chelate heavy metals. Any chelating effect is likely due to its high concentration of selenium, with one nut containing 68-91 mcg of selenium.
7) N-Acetylcysteine Reduces Mercury and Lead Levels
N-Acetylcysteine (NAC) is a form of cysteine that increases the production of glutathione.
In mice, N-Acetylcysteine enhanced excretion of mercury by 400% in comparison to control animals [R].
In 171 workers exposed to lead, N-Acetylcysteine reduced blood levels of lead and increased glutathione concentrations, while at the same time decreasing oxidative stress [R].
8) Zinc Prevents Cadmium and Lead Absorption and Increases Cadmium Excretion
Zinc competes with cadmium and lead for the binding sites on proteins, and zinc deficiency can lead to greater absorption of cadmium and lead [R, R].
Zinc supplementation also increases synthesis of metallothionein, a protein that binds cadmium and helps detoxify it from the body [R, R].
Moreover, supplementation with zinc protects the activity of an enzyme called δ-aminolevulinic acid dehydratase (ALAD) that is very sensitive to lead [R].
9) Calcium Disodium EDTA Increases Lead Excretion
Calcium Disodium EDTA (CaNA2EDTA) is effective in chelating lead from the body [R]. Because it is poorly absorbed orally, EDTA must be administered intravenously.
Caution is needed when chelating with CaNA2EDTA as it tends to deplete essential minerals, particularly zinc, copper, and manganese [R]. It should not be used during pregnancy or in people with kidney or liver diseases [R]
10) DMSA Increases Lead, Mercury, Arsenic and Cadmium Excretion
Dimercaptosuccinic acid (DMSA) is a water-soluble pharmaceutical chelator that contains two thiol groups, making it an especially strong chelator of heavy metals.
It can be administered orally, intravenously, or through the skin.
Chelation therapy is the use of intravenous pharmaceutical chelation agents such as DMSA, dimercaptopropane sulfonate (DMPS), or ethylenediaminetetraacetic acid (EDTA) to pull heavy metals out of the blood in cases of acute toxicity [R].
Chelation therapy is also used to treat cardiovascular disease, but a systematic review found that evidence does not support its use for such diseases [R].
Oral supplementation with DMSA has been shown in many studies to significantly and greatly increase urinary excretion of lead, mercury, arsenic, and cadmium [R, R, R, R].
In 17 lead-poisoned adults, DMSA increased urinary lead excretion by a factor of 12 and rapidly reversed symptoms related to lead toxicity [R].
Caution is warranted with DMSA, as it has also been shown to excrete beneficial metals like zinc, iron, calcium, copper, and magnesium as well, so it strongly advised to supplement with these after therapy [R].
11) DMPS Increases Lead, Mercury, Arsenic, and Cadmium Excretion
Dimercaptopropane sulfonate (DMPS) is another pharmaceutical chelator, like DMSA, with two thiol groups.
Oral absorption of DMPS is about 40% higher than that of DMSA [R].
Like DMSA, DMPS increases excretion of arsenic, cadmium, lead, and mercury in the urine, with the former more effective in excreting mercury from the brain and the latter more effective in excreting mercury from the kidney [R, R, R, R].
In mice, DMSA was more effective in removing cadmium than DMPS [R].
Also like DMSA, DMPS increase urinary excretion of necessary nutrients like copper, selenium, zinc, and magnesium, necessitating supplementation with them before or after treatment [R].
In one trial with autistic patients, a few children developed worsening of symptoms [R]. The researchers thought that this was likely due to the redistribution of recently mobilized metals without the ability to excrete them sufficiently [R].
In addition, adequate hydration and bowel regularity are essential, as during chelation therapy, mobilization and chelation of metals should not exceed the ability to excrete them, otherwise they will be redistributed throughout the body where they have the potential to cause more harm than their initial storage site.
Chelating Compounds With Non-Human Evidence
Garlic has been shown to protect against the damaging effects of heavy metals and help with their excretion.
When rats were given garlic at the same time as cadmium and mercury, accumulation of the heavy metals in the liver, kidneys, bone, and testes was decreased and the activity of certain key enzymes was partially restored [R]. In addition, cadmium excretion was increased.
In rats given mercury, cadmium, and lead in addition to 7% raw garlic in their food, accumulation of the heavy metals was decreased in the liver, with the greatest effect seen for cadmium [R].
In mice, diets consisting of 5% and 10% of Chlorella significantly increased urinary and fecal excretion of mercury, and decreased mercury levels in the brain and kidneys, without affecting glutathione levels [R].
In mice, cilantro supplementation alongside lead administration resulted in significantly fewer lead deposits in the bones [R].
In humans, a study (RCT) on 32 children aged 3-7 years with lead-exposed parents found that cilantro extract given for 14 days decreased lead concentration in blood while increased its excretion in urine. However, it didn’t increase significantly more than the placebo group [R].
While there are studies showing activated charcoal’s ability to bind mercury, lead, and nickel in industrial waste, no studies that have measured its chelation abilities in the human body [R].
Methionine may help with chelating metals because of its sulfur group.
When methionine was added to the diet of rats, it significantly increased fecal excretion of lead [R].
Taurine is a sulfur-containing compound.
When taurine was given to mice, it protected against oxidative damage in the brain caused by cadmium and improved the antioxidant status in the animals [R].
Another study in rats found that taurine supplementation prevented damage of brain tissue due to arsenic [R].
Taurine has also been shown to protect against lead toxicity in rat ovaries and mercury toxicity in the hearts and livers of rats, without affecting excretion of either metal [R, R, R].
Carnosine is a molecule made of the amino acids beta-alanine and histidine with strong antioxidant properties [R].
Carnosine is able to chelate cadmium and mercury and prevent heavy metals from harming cell membranes [R].
In rats, carnosine supplementation was able to prevent kidney damage from lead and increased glutathione levels [R].
Other Supplements That May Be Effective:
Experiences of People who Removed Heavy Metals from their Bodies
Many users have reported that N-Acetylcysteine supplementation improves symptoms of depression, reduces brain fog, and provides a slight energy boost. I supplement with N-Acetylcysteine regularly, but I do not exceed 1 g/day as I tend to experience gastrointestinal discomfort and headaches beyond this dosage, which I suspect are due to increased mobilization of metals exceeding my ability to excrete them.
Users report mixed results when supplementing with alpha-lipoic acid, with some noting increased energy and feelings of general well-being and reduction in nerve pain, while others report an increase in fatigue and mental fogginess, to which some attribute to redistribution of mercury.
One individual claimed to have removed heavy metals by taking 1 g/day of DMSA (in addition to N-Acetylcysteine and alpha-lipoic acid) for 3 days every 2 weeks, which eliminated chronic Candida infections and persistent anxietyand brain fog. Another DMSA user noted that just 50 mg of DMSA resulted in psychosis lasting for a month.
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