Heavy metals (including lead, cadmium, mercury, and the metalloid arsenic) are persistent in the environment and have documented potential for serious health consequences. Heavy metal toxicity may damage:

• central nervous system
• cardiovascular system
• gastrointestinal system
• lungs
• kidneys
• liver
• endocrine glands
• bones

Fortunately, integrative interventions like selenium and garlic have been shown to decrease the buildup and increase the excretion of toxic heavy metals.

Risk Factors for Toxic Metal Exposure

Lead:

• Lead-containing plumbing
• Lead-based paints (in buildings built before 1978 and is the predominant source for children)
• Foods grown in lead-rich soil

Mercury:

• Eating fish or shellfish contaminated with methylmercury (includes shark, swordfish, king mackerel, tile fish, bass, walleye, pickerel)
• Breathing contaminated workplace air or skin contact during use in the workplace
• Release of mercury vapor from dental amalgam fillings

Cadmium:

• Tobacco smoke
• Eating foods containing cadmium (levels are highest in grains, legumes, and leafy vegetables, fish and shellfish)
• Contact with cadmium from household products (electric batteries and solar panels)

Heavy Metal Testing and Toxicity Signs & Symptoms

These can be similar to other health conditions and may not be immediately recognized as due to heavy metal toxicity:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Central nervous system dysfunction
• Heart problems
• Anemia

Diagnosis

• Blood testing
• Urine testing
• Hair and nail analysis

Conventional Treatment

• Chelation therapy, which enhances the elimination of metals (both toxic and essential) from the body, including:
• DMPS, an oral medication for arsenic, cadmium, and mercury toxicity
• Succimer (DMSA), an oral medication for mild-to-moderate lead, arsenic and mercury toxicity
• Calcium-disodium EDTA for lead encephalopathy and lead poisoning

Novel & Emerging Therapies

• Toxicogenomics, the study of gene expression changes by toxin exposure
• New chelation therapies, including polygamma-glutamic acid-coated superparamagnetic nanoparticles that have a high specificity for metal toxins

Dietary & Lifestyle Changes

• Avoid or replace mercury amalgam dental fillings with mercury-free composite material
• Maintain nutrient sufficiency, as adequate intake of essential trace minerals may reduce toxic metal uptake
• Limit consumption of high-mercury fish to no more than 1 serving/week

Nutrients

• Selenium: Selenium is an inhibitor of mercury accumulation and increases excretion of mercury and arsenic
• Vitamin C: A free-radical scavenger that has been shown to reduce lead levels in humans
• Folate: Higher blood folate levels in pregnant women were associated with lower blood mercury and cadmium levels
• Garlic: Garlic lowered lead levels in the blood of industrial workers as effectively as the chelator D-penicillamine
• Alpha-lipoic acid and glutathione: In preclinical studies, these compounds reduced the adverse changes in blood parameters due to lead, cadmium, and copper

Heavy metals with adverse health effects in human metabolism (including lead, cadmium, and mercury) present obvious concerns due to their persistence in the environment and documented potential for serious health consequences.^1-6

Acute heavy metal intoxications may damage central nervous function, the cardiovascular and gastrointestinal systems, lungs, kidneys, liver, endocrine glands, and bones.^7,8 Chronic heavy metal exposure has been implicated in several degenerative diseases of these same systems and may increase the risk of some cancers.^9,10

Heavy metals are ubiquitous in the environment.¹¹ Humans risk overexposure from environmental concentrations that occur naturally (eg, arsenic-rich mineral deposits) or human activities (eg, lead or mercury release as a result of industrial pollution).^12,13

It is not possible to completely avoid exposure to toxic metals.¹⁴ Even people who are not occupationally exposed carry certain metals in their body as a result of exposure from other sources, such as food, beverages, or air.^15,16 It is, however, possible to reduce metal toxicity risk through lifestyle choices that diminish the probability of harmful heavy metal uptake, such as dietary measures that may promote the safe metabolism or excretion of ingested heavy metals.¹⁷

This protocol will discuss the general features of heavy metal toxicity, with emphasis on the three metals that present the highest risk for environmental exposure and are most frequently implicated in acute toxicities: lead, mercury, and cadmium, as well as the toxic metalloid arsenic. We will also present strategies for minimizing the risk of toxicity.

The term “heavy metal” assumes a variety of different meanings throughout the different branches of science. Although “heavy metal” lacks a consistent definition in medical and scientific literature, the term is commonly used to describe the group of dense metals or their related compounds, usually associated with environmental pollution or toxicity.¹⁸ Elements fitting this description include lead, mercury, and cadmium. The rather broad definition of heavy metals may also be applied to toxic metalloids (a chemical element that has properties that include a mixture of those of metals and non-metals), like arsenic, as well as nutritionally-essential trace minerals with potential toxicities at elevated intake or exposure (eg, iron, zinc, or copper).^18,19

Although “heavy metal” toxicities due to lead, mercury, and cadmium are generally considered rare in mainstream medicine, less well-recognized is that chronic accumulation that may not achieve classical acute toxicity thresholds may nevertheless contribute to adverse health effects.

Regarding acute toxicity, according to the 2023 National Poison Data System annual report, there were 7905 reported unintentional heavy metal exposures in the United States, resulting in 26 serious health outcomes and two deaths. While data from the National Health and Nutrition Examination Survey (NHANES) and other sources shows a decade of encouraging year-over-year decreases in acutely toxic heavy metal exposure in the United States, there are still a significant number of people with blood levels that may put them at risk for chronic accumulation, and therefore toxicity, over time.^20-22 For example, in the United States, children are exposed to lead in at least 4 million households. Children are particularly sensitive to lead intoxication, both acute and chronic, and there is no identified safe level of lead exposure in children.^23-25 Further, pregnant women risk toxic exposure to the developing fetus since the mobilization of stored lead from the mother’s bones can leach into the bloodstream, and this is more likely the result of chronic rather than acute lead exposure in the mother.²⁶ With several toxic metals lacking robust pathways for elimination or otherwise remaining in the body for along time, body burdens of some toxic metals (eg, lead, mercury, cadmium) may increase with age.²⁷

While a specific toxic metal has the potential to exert detrimental effects by select mechanisms, there are several common features among toxic heavy metals. One of the most widely studied mechanisms of action for toxic metals is oxidative damage due to direct generation of free radical species and depletion of antioxidant reserves.²⁸ Mercury, cadmium, and lead, for example, can effectively inhibit cellular glutathione peroxidase, reducing the effectiveness of this antioxidant defense system for detoxification.²⁹ Many toxic heavy metals act as molecular “mimics” of nutritionally essential trace elements; as a result, they may compete with essential metallic cofactors for entry into cells and incorporation into enzymes.⁷ For example, cadmium can compete with and displace zinc from proteins and enzymes; lead is chemically similar to calcium; and thallium is a potassium mimic in nerves and the cardiovascular system.^7,30,31

The severity and health outcomes of toxic heavy metal exposure depend on several factors, including the type and form of the element, route of exposure (oral/inhalation/topical/ocular), duration of exposure (acute vs. chronic), and a person’s individual susceptibility.^32-34

Acute toxicities arise from sudden exposures to substantial quantities of some metals (such as from occupational exposure to aluminum dust or breaking a mercury-containing thermometer) and typically affect multiple organ systems, commonly the gastrointestinal tract, cardiovascular system, nervous system, endocrine system, kidneys, hair, and nails.⁷ Acute exposures to some metals (mercury, gold, nickel, and others) can also cause hypersensitivity (allergic) reactions.³⁵

Chronic toxicities are manifested as conditions that develop over extended periods from chronic exposure to relatively low concentrations (eg, sustained environmental exposure). Symptoms of chronic heavy metal toxicity (described later in this protocol) can be similar to other health conditions and may not be immediately recognized as intoxications. Increased cancer risk is a common feature of chronic exposure to certain metals; the exact mechanism of their carcinogenicity is not completely understood, although many are weak mutagens (cause DNA damage), can disrupt gene expression, and deregulate cell growth and development.⁹ They can also interfere with innate DNA repair systems.³⁶ In addition, certain metals may affect gene expression and alter gene function.^37,38

The International Agency for Research on Cancer (IARC) has classified several metals based on their potential carcinogenicity to humans. Group 1 metals include arsenic and arsenic compounds, cadmium, and nickel compounds. Group 2B (possible carcinogens) include cobalt and cobalt compounds.^9,35

Mercury

Mercury has no known beneficial role in human metabolism, and its ability to affect the distribution and retention of other heavy metals makes it one of the most dangerous toxic metals.³⁹ Mercury toxicity can arise from ingestion of metallic mercury or mercury salts (which are generally poorly bioavailable) or by inhalation of mercury vapor (which is readily absorbed).⁴⁰ The relatively high solubility and stability of certain mercury salts in water enables them to be readily taken up and biotransformed to methylmercury by certain fish; these forms are readily absorbed through the gastrointestinal tract and are becoming a major source of mercury exposure in humans.³⁹ Dimethylmercury, a mercury compound chemically synthesized in the laboratory, can also be absorbed through the skin, and several cases of fatal exposure among laboratory workers have been reported.^41,42

Although humans can excrete small amounts of mercury in urine or feces as well as via exhalation or sweating, they lack an active robust mechanism for mercury excretion, allowing levels to accumulate with chronic exposure.^39,43 Mercury, particularly when inhaled as mercury vapors, can distribute to many organs, but may concentrate in the brain and kidneys.⁶ It can also cross the placenta and be found in breast milk.⁴⁴

Mercury exerts its toxic effects by competing with and displacing iron and copper from the active site of enzymes involved in energy production; this induces mitochondrial dysfunction and oxidative damage. Mercury can also directly accelerate the oxidative destruction of cell membranes and low-density lipoprotein (LDL) cholesterol particles as well as bind to and inactivate the cellular antioxidants N-acetyl cysteine, alpha-lipoic acid, and glutathione.³⁹ Because of its effect on cellular defense and energy generation, mercury can cause widespread toxicity and symptoms in several organ systems: nervous system (eg, personality changes, tremors, memory deficits, loss of coordination); cardiovascular system (eg, increased risk of arterial obstruction, hypertension, stroke, atherosclerosis, heart attacks, and increased inflammation); gastrointestinal tract (eg, nausea, diarrhea, ulceration); and kidneys (failure).^6,39 Mercury may also accumulate in the thyroid and increase the risk of autoimmune disorders,⁴⁵ and may cause contact dermatitis.⁴⁶

Lead

Lead toxicity is one of the most frequently reported unintentional toxic heavy metal exposures and the leading cause of single metal toxicity in children.¹⁹ Lead has no known beneficial function in human metabolism. Human environmental exposure is often through lead-containing paint, food stored in lead can liners, food stored in ceramic jars, or contaminated water (pipes cast in lead or soldered using lead solder). Inhalation of lead particulates is a primary route of occupational lead exposure, while oral ingestion is a primary form of exposure in the general population.^3,47 Animal models also suggest that lead can be absorbed through the skin; lead acetate can be found in some cosmetic products.³ Children absorb lead up to 8-times more efficiently than adults.⁴⁸ Ingestion of deteriorating lead-based paint chips or dust is the primary source of lead exposure in children.^49,50 Also, toys and other children’s products may contain lead or be painted with lead-based paint; imported children’s products pose greater risk.^51-53 In 2009 and 2011, the Consumer Product Safety Commission began requiring lower lead levels in children’s products (as of 2011, allowing less than 100 ppm [parts per million] of lead in accessible parts of children’s products with some exceptions)⁵⁴; however, caution is still warranted. Because it mimics calcium, most absorbed lead is stored in the bones of children and adults where it can remain for decades. Conditions that cause release of calcium from the bones (fracture, pregnancy, age-related bone loss) will also release stored lead from bones, thus allowing it to enter into the blood and other organs. Lead can leave the body through feces or urine.³

In addition to disrupting calcium metabolism, lead can mimic and displace magnesium and iron from certain enzymes that construct the building blocks of DNA (nucleotides) and disrupt the activity of zinc in the synthesis of heme (the carrier of oxygen in red blood cells).⁵⁵ Chronic, low-level lead exposure (blood levels <10 µg/dL) is associated with increases in hypertension risk and reduction in kidney function. Higher levels of lead exposure affect the endocrine glands (changing the levels of thyroid hormones [at serum lead levels over 40–60 µg/dL] and reproductive hormones [at serum lead levels over 30–40 µg/dL] and lowering vitamin D levels), brain (causing conditions such as brain lesions, cognitive deficits, and behavioral changes), and can cause anemia. In children, low level (<10 µg/dL) lead exposure can result in several developmental disorders (accelerated skeletal growth, cognitive deficits and IQ decline, slowed growth and delayed sexual maturation) and higher levels (around 60–100 µg/dL) can manifest as colic.³

Cadmium

Acute cadmium intoxication is a potentially fatal, but very rare event¹⁹; chronic exposure to cadmium presents a larger threat to human health.³¹ Cadmium has no known beneficial role in human metabolism. Cadmium is found in soil and ocean water, and up to 10% of the cadmium ingested from dietary sources, such as food and water, is absorbed by the body. It is readily absorbed (40–60%) through the inhalation of cigarette smoke and can be absorbed through the skin. Following exposure, cadmium binds to red blood cells and is transported throughout the body where it concentrates in the liver and kidneys; significant amounts are also found in the testes, pancreas, and spleen.⁵⁶ Cadmium is excreted slowly and may remain in the body for more than 20–30 years.^31,56 As it mimics zinc, cadmium is thought to exert its toxic activity by disrupting zinc metabolism; there are about 3,000 different enzymes and structural proteins in human metabolism that require zinc for their activity and are potential targets of cadmium toxicity.⁵⁶ Cadmium interferes with the cellular balance of zinc, and nutritional zinc or iron deficiencies can increase cadmium absorption.^31,56 Chronic cadmium exposure can result in the accumulation of cadmium complexes in the kidney (potentially leading to renal failure), decreased bone mineralization, and decreased lung function; it is also a known human carcinogen.^{5,31,35,56,57}

Arsenic

Although arsenic is not technically a “heavy metal,” this metalloid (an element with both metal and non-metal chemical characteristics) nevertheless holds significant potential for adverse health outcomes.

In both 2007 and 2011, arsenic topped the Agency for Toxic Substances and Disease Registry (ATSDR) Priority List of Hazardous Substances, which ranks hazardous substances based on their frequency, toxicity, and potential for human exposure from hazardous waste sites.⁵⁸ It is one of the more commonly reported sources of unintentional intoxications.¹⁹ Arsenic occurs naturally in the environment as both inorganic (the less abundant, more toxic form) and organic (the less toxic, more abundant form) arsenic. The most common route of exposure in humans is consumption of arsenic-containing food or drinking water. Seafood contains the highest concentrations of organic arsenic; cereals and poultry are also sources. Arsenic can also be inhaled (the predominant route for occupational exposure) or absorbed through the skin.² Inorganic arsenic binds to hemoglobin in red blood cells once absorbed and is rapidly distributed to the liver, kidneys, heart, lungs, and to a lesser degree the nervous system, gastrointestinal tract, and spleen; it can also cross the placenta.⁵⁹ Some inorganic arsenic can be converted to organic arsenic compounds in the liver (monomethylarsonic and dimethylarsinic acids) that have less acute toxicity.^2,59 Most inorganic and organic arsenic compounds are excreted by the kidneys, with a small amount retained in keratin-rich tissues (eg, nails, hair, and skin).⁵⁹

Arsenic binds and depletes lipoic acid in cells, interfering with the production of chemical energy (adenosine triphosphate [ATP]); it can also directly bind to and inactivate ATP.⁵⁹ Acute exposure to inorganic arsenic may cause nausea, vomiting, profuse diarrhea, arrhythmia, a decrease in red and white blood cell production, loss of blood volume (hypovolemic shock), burning or numbness in the extremities, and encephalopathy.^2,60 Organic forms of arsenic have little acute toxicity compared with inorganic arsenic and arsine gas, the other two chemical forms of arsenic, which are more toxic.⁵⁹ Chronic inorganic arsenic exposure can result in anemia, neuropathy, or liver toxicity within a few weeks to months.^58,59 Longer exposure (3–7 years) can also result in characteristic skin lesions (areas of hyperpigmentation or keratin-containing lesions) on the palms and soles of the feet. Severe exposure can lead to loss of circulation to extremities, which can become necrotic and gangrenous (“black foot disease”).^2,59 Chronic exposure to arsenic has been associated with several types of cancer (skin, lung, liver, bladder, and kidney).⁵⁹ Chronic exposure to dimethylarsinic acid, a form of organic arsenic, may cause kidney damage.²

Other Metals

There are several other metals with documented toxicities and varying risk of unintentional overexposure.

Iron. Iron toxicity is the most common metal toxicity worldwide.^61,62 The classic symptom of iron overload, especially in the context of the disease hemochromatosis, is skin hyperpigmentation (to a bronze or gray color) due to deposits of iron and melanin complexes in the skin. The liver, as a primary source of iron storage, is particularly susceptible to overload and related damage.⁶³ Iron toxicity is also associated with joint disease (arthropathy), arrhythmia, heart failure, increased atherosclerosis risk, and increases in the risk of liver, breast, gastrointestinal, and hematologic cancers.^64-70 A comprehensive overview of iron overload is available in the Hemochromatosis protocol.

Aluminum. Aluminum is ubiquitous in nature (it is the most abundant metal in the earth’s crust) and naturally occurs in most foods and water; daily exposure through food, in most people, is 3–10 mg.^61,71 However, occupational exposure to aluminum can cause significant toxicity, and aluminum toxicities are more frequently reported to poison control centers than are non-pesticide arsenic toxicities.¹⁹ Elevated levels of aluminum in the brains of some Alzheimer patients is of unknown significance as to correlation and cause; data supporting the association is inconclusive, with more studies required to determine if aluminum plays a causal role in Alzheimer disease pathogenesis.^72-74

Copper. Although copper plays an important role in human nutrition, toxicity at elevated exposure has been reported. Excessive copper (through overexposure or from copper metabolism diseases like Wilson disease) can be neurotoxic,⁷⁵ and acute unintentional copper toxicities are more frequently reported than those of arsenic.¹⁹

Miscellaneous. Acute manganese intoxication has also been infrequently reported to U.S. poison control centers.¹⁹ The release of depleted uranium into the environment (from armor-piercing ammunition) in regions like the Balkans and Middle East has been implicated in epidemics of leukemia, Kaposi sarcoma, and severe congenital defects.⁷⁶

Toxic metals can contaminate water, air, soil, and food, and are present in many materials commonly found at home. They can enter the body through the skin, digestive tract, or respiratory system, and such exposures may be acute or chronic.^77,78 The most common cause of heavy metal toxicity is consumption of contaminated food. People who live or work near high-traffic roads or high-polluting industries like mines, smelters, power plants, and agriculture have an increased risk of toxic exposures. Other sources of heavy metal exposure include household pesticides, wood treatment products, paints, cosmetics, cigarette smoke, dental amalgams, medications, medical devices, and electronic devices.⁷⁷

Lead:

A large proportion of lead exposure is related to fossil fuel development, mining, smelting, and other industrial activities.⁷⁸ Restrictions on the use of lead in household and industrial materials like water pipes, paints, food cans, construction materials, and cosmetics, as well as in gasoline for road vehicles, have led to reduced risk of toxicity, especially in developed countries. However, lead-acid batteries and ammunition continue to be sources of lead exposure.^78,79

• Water. Lead has long been used in water distribution systems—so much so that the word “plumbing” is based on the Latin word for lead, plumbum. Lead in pipes, pipe coatings, solder, faucets, valves, and meters, combined with water’s corrosive nature, has made drinking water a major historical source of lead toxicity. Although regulations around lead use in plumbing supplies have resulted in the slow removal of lead from water systems in many countries, drinking water continues to be an underappreciated source of lead exposure in the United States and around the world.⁸⁰
• Soil and food. Lead in the air eventually settles on the ground and persists in soils.⁷⁸ It also settles directly on plants, which then absorb it to varying degrees. Coffee, tea, and cocoa have been found to have higher lead concentrations than vegetables, alcoholic beverages, and grains, but absolute levels depend on the degree of regional soil contamination.⁸¹
• Air. Inhalation of airborne lead is a key route of lead toxicity. Air lead levels have decreased over the last 40 years since the use of lead in gasoline has been reduced worldwide.⁷⁸

Mercury:

Mercury is released into the environment from industrial activities such as smelting and other metal work, coal-fired energy production, waste incineration, cement production, and electronic waste recycling.⁸² It exists in organic and inorganic compounds, as well as in its elemental state. Elemental mercury, known as quicksilver, is a silver-white liquid that slowly evaporates into a colorless, odorless, toxic gas. Although it is no longer used in thermometers and most light bulbs, elemental mercury is still used in tubular fluorescent bulbs, dental amalgams, and as a red pigment, such as in tattoo dye.^78,82 Mercury is also found in some skin creams, cleansers, lighteners, and cosmetics. Mercury from these sources can be absorbed through the skin and cause toxicity.⁸³

• Water and seafood. Inorganic and elemental mercury from coal-fired power plants, electronic waste sites, and other industrial emissions contaminate water. Once in the environment, mercury can form organic compounds like methylmercury, a highly toxic water contaminant that bioaccumulates in fish, especially large predatory fish.^78,83 Seafood consumption is a major source of methylmercury ingestion by humans.^77,78 Baking, grilling, or frying seafood (rather than eating it raw, as in sushi) causes mercury to become less accessible in the digestive tract. In addition, consuming seafood along with tea, coffee, fiber, fruit, garlic, or broccoli appears to reduce methylmercury bioaccessibility.^83-85
• Soil and food. High levels of soil mercury contamination are found in regions near industries with mercury-laden emissions, including fluorescent light manufacturing and electronic waste and recycling sites. It is known to accumulate in food crops, especially rice.^82,86
• Air. Mercury vaporizes, particularly at higher temperatures, becoming a highly toxic air pollutant. When inhaled, it is readily absorbed into circulation and crosses the blood–brain barrier.^78,87 Occupational exposure to mercury vapor, such as in metal industries, electronic device recycling, or working with dental amalgams, can cause dangerous toxic effects.⁷⁷ Once in the mouth, dental amalgams (often referred to as silver fillings) continuously release low concentrations of mercury vapor, causing chronic exposure that has been implicated as a possible contributor to neurodegenerative diseases.^87,88

Arsenic:

Arsenic is present in various types of rock and mineral-rich ores. It is spread in the environment through mining, smelting, fracking, coal burning, and the use of pesticides.⁹¹ Arsenic is also an industrial by-product from processing of materials such as glass, textiles, ammunition, paper, and wood,^78,80 and is used as a pigment in cosmetics like eyeshadow, lipstick, lip balm, foundation, whitening cream, and hair dye. Because arsenic can be absorbed through the skin and cause toxic effects, its use in cosmetics and other skin products is regulated in the United States and some other countries.⁷⁷ Arsenic has historically been added to some traditional Chinese herbal medicines, causing dangerous levels of intoxication.⁷⁸

• Water and seafood. Drinking water is a prominent source of arsenic exposure.⁸¹ Naturally high-water arsenic concentrations can occur in regions with high-arsenic sediments and rock, but most arsenic water contamination is due to industrial activities.^78,92 Arsenic in seafood occurs mainly in organic compounds, which have low toxicity, but more toxic inorganic arsenic compounds can be present in fish, shellfish, and especially seaweed.^81,91
• Soil and food. Soils may be naturally arsenic-rich or, more likely, contaminated by regional industry. Foods grown in contaminated soil are another key source of arsenic exposure.⁹² Rice is especially prone to sequestering arsenic from the environment. Some mushroom species, legumes, and root vegetables can also be arsenic sources.^81,91 Arsenic in milk from cows grazing in high-arsenic regions is a particular concern in infants and children.⁹¹
• Air. Arsenic is released into the air during volcanic and geothermal events.⁹¹ However, inhalation is not considered to be a major source of arsenic toxicity.

Cadmium:

Cadmium, a rare element in rock and mineral ore, is naturally distributed in the environment through weathering and volcanic events; however, most human exposure is due to human activities including mining and processing of other minerals and through industrial use of cadmium such as for metal coatings, chemical stabilization, and in batteries, pigments, and alloys.⁷⁸ Electronic device and battery recycling is a growing source of cadmium exposure.⁹³

• Water and seafood. Agricultural runoff can contaminate water with cadmium.⁷⁷ Shellfish are particularly prone to cadmium accumulation and becoming a dietary source of toxic cadmium.⁸¹
• Soil and food. Industrially released cadmium and cadmium in fertilizers contaminate agricultural soils.⁷⁸ Ingestion of foods grown in high-cadmium soils is the main cause of cadmium toxicity.⁹³ Leafy green vegetables, oilseeds and nuts, potatoes, and rice grown in cadmium-contaminated soils have particularly high cadmium concentrations.⁷⁷ Cadmium is well known to concentrate in tobacco leaves, making tobacco use a major cause of cadmium toxicity.^77,93 Coffee, tea, and cocoa have also demonstrated relatively high cadmium levels, probably due to fertilization practices.⁸¹
• Air. Regions contaminated with cadmium have high levels of cadmium dust, and inhalation is a potential route of toxicity. ^78,93 Cadmium can become aerosolized through burning fossil fuels, mining, mineral ore processing, incinerating waste (especially plastics), and other industrial activities.⁹³

Other Toxic Metals:

Aluminum is found in many household products as well as compounds used in oil refining, photography, and building. Major sources of aluminum contamination of air, water, and soil include coal-fired power plants, steel foundries, and metal refineries. Aluminum is also a component of car emissions; however, absorption in the digestive tract is the main route of aluminum toxicity in humans. Aluminum can be transferred to food via cookware, food wrapping for storage, and cooking food in aluminum foil. Aluminum contamination of food is enhanced by increased temperature, duration of contact, and food acidity and fat content. Aluminum is eliminated very slowly and can accumulate in tissues, causing toxic effects over years.⁷⁸

Uranium is a naturally occurring radioactive element found in the earth’s crust. Occupational exposure to radioactive uranium byproducts can occur in workers involved in production of certain military and medical equipment.⁸⁰ While there is much awareness about toxicity from its radioactivity, its non-radiotoxic effects may be underappreciated.⁹⁴ Drinking water is the main source of toxic uranium exposure in the United States, but uranium can also contaminate air, soil, and food. Uranium mining is associated with higher regional levels, putting nearby communities at increased risk of uranium toxicity. Fertilizer production and military activity have also been reported to increase uranium water contamination.⁸⁰

Chromium is a micronutrient found in various foods and supplements that supports healthy glucose and lipid metabolism. Chromium in rock, soil, and ore is generally found in its trivalent form (chromium [III]), which is the form used in supplements. However, industrial processing can produce oxidized, hexavalent chromium (chromium [VI]), which is toxic. Chronic toxicity may be linked to occupational chromium use, such as for chrome plating, steel welding, leather tanning, wood treatment, and other industrial activities. In addition, people living in the vicinity of such industry are at risk of toxic hexavalent chromium exposure due to air, water, and soil contamination.^77,78

Cobalt, nickel, and manganese are essential trace minerals found in small amounts in foods such as fish, leafy greens, and chocolate; however, chronic exposure to high levels can cause toxic effects. Cobalt, nickel, and manganese are commonly used in metal alloys with a broad array of applications. They can become aerosolized due to industrial activity, leading to their inhalation. They can also be absorbed through the skin via direct contact.⁹⁵

Acute and Chronic Health Effects

Heavy metal toxicity encompasses a wide spectrum of clinical manifestations that vary according to metal type, dose, exposure duration, and patient age.¹⁰⁴ Heavy metal toxicities are commonly categorized as acute or chronic, reflecting differences in exposure patterns and resulting clinical presentations.³² Heavy metals exert toxic effects through oxidative stress, inhibition of beneficial enzymatic activity, and displacement of essential metals such as calcium, zinc, and iron.¹⁰⁵

Acute heavy metal toxicity refers to sudden, significant exposures and typically presents rapidly with multi-organ involvement and may lead to death if untreated.^32,104 Symptoms vary by metal but frequently include gastrointestinal, cardiovascular, and neurologic disturbances. For example:

• Arsenic poisoning often causes profuse watery diarrhea resembling “rice water,” severe nausea, vomiting, hypotension, and life-threatening arrhythmias.¹⁰⁴
• Manifestations of acute mercury toxicity depend on the exposure route: inhalation may cause cough, shortness of breath, chest tightness, and pneumonitis, while ingestion may cause gastrointestinal bleeding and abdominal pain.⁷⁸
• Lead exposure can lead to abdominal colic, confusion, encephalopathy, anemia, and, in children, seizures.¹⁰⁴
• Acute cadmium inhalation may trigger “metal fume fever,” progressing to pulmonary edema, hypoxia, and, in severe cases, respiratory failure.^106,107

If you have been recently exposed to heavy metals, and are experiencing any of the above symptoms, go to the nearest emergency room. For additional guidance, contact a poison control center.

Chronic heavy metal toxicity develops gradually over months to years, often due to occupational or environmental exposure, and frequently goes unnoticed because of nonspecific, slowly evolving symptoms.^104,106

• Chronic lead poisoning may cause fatigue, irritability, cognitive decline, anemia, peripheral neuropathy, and dark gingival “lead lines.” Lead also disrupts hemoglobin synthesis, leading to the development of anemia, and contributing to long-term neurological effects.¹⁰⁶
• Long-term mercury exposure may present with symptoms such as tremors, memory loss, insomnia, and nerve pain, as well as subtle mood changes including irritability, shyness, mood swings, and social withdrawal.¹⁰⁶
• Chronic arsenic toxicity can cause progressive skin hyperpigmentation, palmar keratoses, Mees’ lines (horizontal white lines that run across the nails), and peripheral nerve pain, while also elevating cancer risk. Vascular complications, such as peripheral vascular disease and Raynaud-like symptoms, may precede dermatologic changes.¹⁰⁸
• Prolonged cadmium exposure impairs kidney function and can lead to protein loss in the urine and bone problems. Chronic cadmium exposure can also reduce lung capacity and cause emphysema.^106,107

Diagnosing Heavy Metal Toxicity

Due to its nonspecific nature, heavy metal toxicity requires a systematic approach. Early symptoms such as abdominal pain, fatigue, or cognitive changes may mimic other disorders, delaying recognition until more severe findings appear (eg, neuropathy, organ dysfunction, or malignancy).^78,104 A thorough exposure history is critical, including occupational risks (eg, battery work, welding, mining), dietary intake (eg, large predatory fish), housing and water conditions, and imported goods such as ceramics, cosmetics, and jewelry, especially from countries frequently linked to contamination such as China, India, Turkey, Vietnam, and Mexico.^106,109 Physical exam findings may provide clues—such as lead-related Burton’s lines (dark blue-black lines that appear along the gums), Mees’ lines (typically associated with arsenic or mercury poisoning), or arsenic-related hyperkeratosis (abnormally thick, rough patches of skin, especially on the palms and soles)—but they are not specific nor consistently present.^104,106 Laboratory testing confirms exposure, with blood and urine best for recent or ongoing exposure, and keratin-rich tissues (hair, nails) better for long-term accumulation.¹¹⁰ Several methods to detect exposure are currently under investigation, including: fecal, salivary, dental, placental, and kidney/liver tissue testing.¹¹⁰

Blood testing is a widely used method for evaluating heavy metal exposure. Whole blood is considered a reliable biomarker for several metals—including lead, mercury, arsenic, and cadmium—because it can reflect both recent exposures and, in some cases, longer-term body burden.^110,111 Commercial blood tests are available for universally toxic metals (eg, lead, mercury) as well as essential metals that are harmful above threshold levels (eg, iron, copper).

Blood levels of cadmium and lead are usually indicative of recent exposure but may not reflect total body burden.³ For lead, blood levels represent exposure only over the previous 90 days, while for arsenic, which is rapidly cleared, blood tests are reliable only during early intoxication (<7–10 days after exposure) and require form-specific analysis to distinguish toxic inorganic forms.^3,60,110 Blood testing is also useful for monitoring dietary methylmercury exposure, although results must be interpreted in the context of exposure timing, genetic and nutritional influences on metabolism, and redistribution from storage sites. However, some metals, such as aluminum, show poor correlation between blood levels and overall exposure.⁴

Urine testing is another common method for assessing heavy metal exposure by measuring excretion of metals including arsenic, mercury, and cadmium.¹¹⁰ Unprovoked urine tests reflect recent exposure by measuring metals excreted under normal conditions, and are widely accepted for clinical and occupational monitoring of heavy metal exposure. Provoked urine tests, on the other hand, involve administration of a chelating agent to mobilize stored metals prior to testing. Although provoked testing may reveal hidden body burdens, the results are highly variable, lack standardized reference ranges, and are generally not recommended.^110,112,113

Imaging studies may also be helpful in selected cases. Radiographs can detect radiopaque lead paint chips or other ingested fragments, particularly in pediatric patients. Computed tomography (CT) and magnetic resonance imaging (MRI) may be employed to evaluate organ damage, cerebral edema, or calcifications related to chronic exposures.¹⁰⁶ While not diagnostic on their own, imaging results contribute to the overall assessment and may help identify complications that guide management.

X-ray fluorescence (XRF) has emerged as a valuable non-invasive technique for assessing heavy metal burden in humans. By irradiating biological samples with focused X-rays, XRF detects the characteristic secondary X-rays emitted by specific atoms, allowing for precise elemental mapping of metals within tissues at high spatial resolution.¹¹⁴ This approach enables simultaneous multi-element analysis, making it especially useful for studying toxic metals such as lead, arsenic, mercury, and cadmium, which accumulate in different tissues and can contribute to disease processes.³ In the field of biomarker research, bone XRF has been applied as a direct indicator of cumulative exposure to lead and other metals, complementing more traditional biomarkers like blood and urine that reflect recent exposure.³

Challenges & Limitations with Testing for Heavy Metal Toxicity

Despite their value, these tests are not without limitations. Blood and urine concentrations fluctuate and may decline rapidly after acute exposure, underestimating total tissue burden. Hair and nail testing can provide a historical record, but results may be confounded by external contamination, such as contact with metal-containing dusts, dyes, or shampoos. Similarly, fecal testing may be influenced by dietary intake rather than true tissue accumulation.¹¹⁰ Because of these challenges, results are often interpreted in combination with one another and correlated with the clinical picture to improve diagnostic accuracy.¹⁰⁴

Ultimately, diagnosis relies on a stepwise integration of exposure history, physical examination, laboratory confirmation, and functional or imaging studies.¹⁰⁴ No single test is definitive in isolation. Instead, clinicians must piece together multiple sources of evidence to distinguish heavy metal toxicity from other conditions with similar presentations. This structured approach ensures not only identification of the offending agent but also assessment of the degree of systemic injury. The specific methods available to diagnose heavy metal toxicity are examined in Table 1.

Table 1. Detection Methods: Human Exposure to Heavy Metals

Removal of Exposure Source

The first step in mitigating the toxic effects of acute or chronic metal exposure is removal of the source of contamination. For acute exposures, this may involve (depending on the route of exposure) decontaminating the area of exposure, removing contaminated clothing, and/or removing the individual from the area where exposure occurred.¹¹⁷

Gastrointestinal Decontamination

Gastrointestinal decontamination techniques may be indicated for acute metal toxicities, although studies on their efficacy for this purpose are lacking and few consensus guidelines exist for their use in acute metal toxicity treatment. Gastric lavage (introduction of water into the stomach by a tube to wash out its contents) has been used in arsenic and lead poisonings.^3,46,60,118 Emesis (induced vomiting) has also been suggested for removing metals within the stomach; however, some caustic metal compounds (mercuric oxide) may cause further damage by induced vomiting,⁶ and emesis is not always effective for removing large amounts of solids.¹¹⁹ Bowel irrigation (introduction of water into the bowel to wash out its contents) may be useful for macroscopic particles of some metals (such as lead) that can easily transit through the intestines; larger particles may require surgery for removal.^60,119-123 Activated charcoal may be effective for binding some ingested toxic metals or metal compounds (arsenic, thallium) but is ineffective for others (iron and mercury).^60,119-123

Chelation Therapy

Chelators enhance the elimination of metals (both toxic and essential) from the body. Their use to ameliorate metal toxicity has been validated by several human case reports and animal models. They are most often used in cases of acute intoxications; the efficacy of chelation therapy in chronic metal intoxication is less clear, as chelation therapies are more effective when administered close to the time of exposure.⁷ The decision to chelate should be made by professionals with experience using chelation therapy, preferably in consultation with a poison control center or medical toxicologist.

Chelators currently used in the United States include:

DMPS. DMPS is an oral medication studied for arsenic and cadmium chelation in animal models^124,125 and mercury chelation in mine workers.⁴² The dosage used in the human trial was 400 mg/day for 14 days. At the end of two weeks, DMPS significantly increased urinary excretion of mercury and improved toxicity symptoms; however, it did not alter blood mercury levels. Allergic rash was the only side effect noted.

Succimer (DMSA). DMSA is an oral medication used to treat mild-moderate lead toxicosis (acute or chronic) in children and adults as well as acute arsenic or mercury intoxication. For both lead and mercury intoxication in adults, DMSA is dosed at 10 mg/kg three times daily for five days, followed by 10mg/kg twice daily for 14 days. Side effects are mostly gastrointestinal (diarrhea and vomiting), metallic taste, and mild increase in liver enzymes; rash, chills, and decreased white cell counts have also (rarely) been reported.⁷

Prussian blue. Prussian blue is an oral chelator for thallium or cesium poisoning in adults and children; it is dosed three times per day. Side effects include constipation, abdominal pain, and a blue color of the stool.⁷

EDTA. Calcium-disodium EDTA is used to treat lead encephalopathy and moderate lead poisoning.^7,126 It is given by slow, continuous intravenous infusion. Side effects include malaise, headache, fatigue, chills or fever, myalgia, anorexia, nasal congestion, watery eyes, anemia, transient hypotension, clotting abnormalities, and kidney failure.⁷ EDTA, particularly after prolonged treatment, can also chelate essential trace metals, such as zinc, copper, and manganese.¹¹⁷ Sodium EDTA (without calcium) can cause life-threatening hypocalcemia.¹²⁷

Penicillamine (Cuprimine). Penicillamine has been used as an oral treatment for lead, mercury, and copper poisoning; its use has fallen out of favor due to its potential for serious complications, which include allergic reactions (seen particularly in people allergic to penicillin), a severe form of anemia, severe lowering of white blood cell counts, and kidney failure.⁷

Iron chelators. There are several iron chelators that have found use in the treatment of metabolic iron overload (hemochromatosis) as well as acute iron intoxication (such as iron supplement overdose). Deferoxamine mesylate (Desferal) is an injectable iron chelator that can remove iron from abnormal tissue stores but not sites of active metabolic iron usage (such as transferrin or hemoglobin).³⁵ Side effects include skin rash, hypotension, respiratory distress, and eye/ear toxicity; acute neurological toxicity is also possible.^35,61 Oral iron chelators include deferiprone (Ferriprox) and deferasirox (Exjade). They have better distribution than deferoxamine, which also increases their toxicity.¹²⁸ Long-term (6-month) deferoxamine treatment has been used to treat aluminum intoxication³⁵ and aluminum-related osteomalacia.⁶¹

Toxicogenomics

While elevated blood levels of metals are associated with adverse health outcomes, they are not necessarily indicative of clinical metal toxicity. Similarly, metal toxicities can occur in some individuals below levels that are predicted to be “safe.” Toxicogenomics, the study of gene expression changes by toxin exposure, may prove to be a useful tool for more sensitive and quick metal toxicity assessment. Several laboratories have already identified specific gene expression patterns in specific tissues arising from environmentally significant toxic metals (such as decreased expression of cytochrome P450 detoxification enzymes in response to arsenic exposure or induction of protective heat shock proteins by cadmium).¹²⁹

Chelation Therapies

Current chelation therapy uses chemical chelators that have several adverse effects, such as kidney overload, cardiac arrest, mineral deficiency, and anemia. This has motivated the search for safer heavy metal chelators, which have desirable properties, high specificity for metal toxins, and low affinity for nutritionally essential metals. Interesting candidates include polygamma-glutamic acid-coated superparamagnetic nanoparticles¹³⁰ and magnetic chitosan/graphene oxide composites,¹³¹ which are both highly selective for lead. Magnetic chelators have the additional advantage that they can be magnetically directed to specific organs of interest.¹³⁰

Maintain Good Occupational Hygiene

Occupational exposure can be reduced by modifying manufacturing processes to reduce worker contact with metal toxins, collecting and removing fumes, following proper hazardous waste management procedures, and substituting with safer materials/procedures when possible. In most countries, regulations limit employee exposure to toxins and establish worker and workplace health surveillance guidelines. Individuals can be proactive by learning about substances they are coming in contact with, limiting exposure by following safety procedures and wearing the required personal protective equipment, practicing proper skin and hand hygiene, and properly decontaminating before leaving the workplace.¹³²

Reduce General Exposure

Exposure to metal toxins can also be reduced by understanding the sources of metal exposure (see the section on risk factors) and adopting strategies to reduce contact with them. First, become familiar with symptoms of toxicity and first aid procedures for ingestion of substances containing toxic metals.¹³³ Next, read product labels and know the potential hazards of products. Third, take advantage of established disposal programs and facilities for discarding metal-containing waste. Finally, avoid mercury amalgam dental fillings to reduce mercury exposure, especially when multiple fillings are needed. In one study, individuals with seven or more mercury fillings had 30–50% higher urinary mercury levels compared to individuals without any amalgam fillings.¹³⁴ Since studies have shown that exposure to mercury via dental amalgam fillings poses health risks,¹³⁵ removing and replacing existing dental fillings with mercury-free composite material should be considered. Individuals seeking to have their mercury amalgam fillings removed and replaced should seek out a dentist experienced in this procedure, as mercury vapor levels can rise in the surrounding environment if proper procedures are not followed during their removal, potentially exposing both the patient and dental staff to excessive mercury.¹³⁶

In addition to the integrative interventions outlined in this protocol, readers are encouraged to review the Metabolic Detoxification protocol, as ensuring that the body’s general intrinsic detoxification pathways are functioning optimally may help avoid heavy metal accumulation and toxicity.

Several dietary constituents have been investigated for their ability to mitigate metal toxicity. They work by reducing or inhibiting metal absorption from the gut, binding up toxic metals in the blood and tissues to help draw them out of the body, or reducing free-radical damage (a significant contributor to the pathology caused by heavy metals). Most studies have been limited to animal and cell culture models, although the results of human studies have been encouraging.

For additional information on nutritional strategies to address iron toxicity, refer to Life Extension’s Iron Overload (Hemochromatosis) protocol.

Maintain Nutrient Sufficiency

Since many toxic metals mimic nutritionally essential metals, they compete for the same transport mechanisms for absorption from the intestines and uptake into cells. Therefore, adequate intake of essential trace minerals may reduce toxic metal uptake. For example, nutritional zinc or iron deficiency can increase cadmium absorption,³¹ and lead absorption from the gut appears to be blocked by calcium, iron, and zinc.^3,137 In animal models, selenium blocks the effects of lead when administered before exposure and reduces mercury toxicity.¹³⁷ It also increases its excretion in humans.^138,139

Choose Fish Oil Supplements over High-Mercury Fish

Most toxicology data support the recommendation, in non-pregnant adults, to limit consumption of high-mercury fish (shark, swordfish, king mackerel, tilefish) to no more than one serving (7 oz.) per week. The Environmental Protection Agency recommends that pregnant women, nursing mothers, and young children avoid eating high-mercury fish because the fetal brain is more sensitive to mercury toxicity than the adult brain.¹⁴⁰ High-quality fish oil supplements represent a good alternative source of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]).¹⁴¹

The International Fish Oil Standards Program (IFOS) is an organization dedicated to differentiating high-quality fish oil products from those of lesser quality. In order to ensure your fish oil supplement does not contain dangerous concentrations of contaminants such as heavy metals, check the label to ensure your fish oil supplement achieves the rigorous IFOS 5-star rating.¹⁴²

Selenium

In addition to its role as a possible competitive inhibitor of mercury and lead absorption, selenium also increases toxic metal excretion. Moderate (100 mcg/day) increases in dietary selenium increased urinary excretion of stored mercury in long-term mercury-exposed Chinese residents,¹³⁸ and 100–200 mcg/day reduced blood and hair levels of arsenic in Chinese farmers with arsenic poisoning.¹³⁹ Selenium also appears to mitigate the toxicity of some heavy metals, such as cadmium, thallium, inorganic mercury, and methylmercury, by modulating their interaction with certain biomolecules.¹⁴³ In another study, supplementation with 100 mcg of selenium (in the form of selenomethionine) daily for four months led to a 34% reduction in levels of mercury detected in body hair. The authors of the study concluded that “… mercury accumulation in [… body] hair can be reduced by dietary supplementation with small daily amounts of organic selenium in a short range of time.”¹⁴⁴

Modified Citrus Pectin

Three studies have investigated the use of modified citrus pectin (MCP) on the mobilization of metals from body stores. In the first, eight healthy individuals were given 15 grams of MCP daily for five days and 20 grams of MCP on day six. Significant increases in urinary excretion of arsenic, mercury, cadmium, and lead occurred within one to six days of MCP treatment. There was a 150% increase in cadmium excretion and a 560% increase in lead excretion on day six.¹⁴⁵ Essential minerals such as calcium, zinc, and magnesium were not noted to increase in the urinary analysis. Second, in a series of case reports, five patients with different illnesses took MCP alone or in combination with alginate for up to eight months. The patients showed a 74% average decrease in toxic heavy metals after treatment.¹⁴⁶ In a third trial, seven children with blood lead levels >20 µg/dL received 15 grams MCP daily for two to four weeks; blood lead levels dropped an average of 161% and urinary lead excretion increased by an average of 132%.¹⁴⁷

Silicon

Data from preliminary human studies reveal that naturally-occurring dissolved silicon from mineral waters appears to antagonize the metabolism of aluminum, potentially reduce Alzheimer risk, and support cognitive function.¹⁴⁸ In human subjects, soluble silicon (orthosilicic acid) decreases aluminum absorption from the digestive tract and decreases its accumulation in the brain.¹⁴⁹ In one study, Alzheimer patients drank up to 1 liter of mineral water daily (containing up to 35 mg of silicon/L) for 12 weeks. Over the study period, urinary excretion of aluminum increased without affecting urinary excretion of the essential metals iron and copper. In addition, there was a clinically relevant improvement in cognitive performance in at least three out of 15 individuals.¹⁵⁰

Another source of orthosilicic acid studied for their metal reducing properties are compounds called zeolites—aluminum/silicon oxide-based crystalline compounds with adsorbent properties that have broad industrial applications and are finding applications in medicine.^151,152 Inclusion of zeolite (as the zeolite clinoptilolite) in high-lead diets of laboratory mice reduced tissue lead concentration by 77–91%, increased the percentage of healthy red blood cells, and reduced chromosomal damage.^152,153 A clinical study on 33 men evaluated the ability of the zeolite clinoptilolite to increase heavy metal urinary excretion.¹⁵⁴ To be included in the trial participants had to test positive, above a predetermined threshold, for at least four of the nine metals in a urinary test panel (ie, aluminum, antimony, arsenic, bismuth, cadmium, lead, mercury, nickel, and tin). The men were given either 15 drops of a clinoptilolite water suspension or placebo suspension twice daily for a maximum of 30 days. Significant increases in the urinary excretion of all nine metals were observed in the men taking clinoptilolite as compared to placebo without a negative impact on electrolyte profiles. It has been hypothesized that the biological activity of some zeolites may be attributed to their orthosilicic acid releasing properties (ie, they are a source of orthosilicic acid).¹⁴⁹

Vitamin C

Vitamin C is a free-radical scavenger that can protect against oxidative damage caused by lead,¹³⁷ mercury,¹⁵⁵ and cadmium¹⁵⁶; it may prevent the absorption of lead as well as inhibit its cellular uptake and decrease its cellular toxicity.¹³⁷ Observational data suggest an inverse relationship between serum levels of ascorbic acid and blood levels of lead; in other words, the higher the blood levels of vitamin C the lower the blood levels of lead.¹⁵⁷ Vitamin C supplementation (500 mg/day) in 12 silver refiners with high blood lead levels (mean of 32.8 µg/dL) demonstrated a 34% reduction in lead levels after one month.¹⁵⁸ In a small study of 75 male smokers, vitamin C (1,000 mg/day) reduced blood lead levels by 81% after one week of supplementation. Lower dose vitamin C (200 mg/day) had no effect.¹⁵⁹

Vitamin E

Through its antioxidant action, vitamin E mitigates some of the toxic damage caused by heavy metals, which are strong inducers of oxidative stress in tissues. In one study, rats were fed a diet containing lead acetate and subsequently developed signs of toxicity such as oxidative damage to lipids and alterations in blood chemistry parameters. When either vitamin E or garlic oil were administered in conjunction with the lead, the toxic effects were ameliorated. The researchers who conducted the study noted that the protective effect of vitamin E was probably due to its ability to support detoxification and scavenge tissue-damaging free radicals.¹⁶⁰ In another animal study, one group of mice were given toxic heavy metals (lead, mercury, cadmium, and copper) in their drinking water for seven weeks, while another group underwent the same treatment but, in addition, received vitamin E five times weekly. The scientists found that the mice not receiving vitamin E exhibited evidence of oxidative injury to their kidneys and testis, whereas those organs appeared normal in mice receiving vitamin E. Also, the mice not receiving vitamin E showed changes in plasma levels of creatinine, urea, and uric acid while these blood parameters did not change significantly in the vitamin E group.¹⁶¹ Vitamin E has also been shown to counter the deleterious effects of heavy metals in humans. In several groups of workers regularly exposed to airborne heavy metal toxicity due to the nature of their work, daily supplementation with 800 mg vitamin E and 500 mg vitamin C for six months led to improved markers of intrinsic antioxidant defenses and decreased markers of oxidative damage. In fact, following the period of supplementation, the activity of certain intrinsic antioxidant systems reached levels comparable to those observed in control subjects not exposed to the toxicants.¹⁶²

Folate

Folic acid is a cofactor in sulfur-containing amino acid metabolism. Sulfur-containing amino acids (cysteine and methionine) are precursors to known heavy metal chelators (alpha-lipoic acid and glutathione). In a study of 1,105 pregnant women, 841 of which were followed through late pregnancy or delivery, higher blood folate levels were associated with lower blood mercury levels during mid- and late-pregnancy.¹⁶³ A similar study in Australia on 173 pregnant non-smokers demonstrated that the failure to use folic acid or iron supplements during pregnancy was associated with higher blood cadmium levels.¹⁶⁴

Garlic

Garlic contains many active sulfur compounds derived from cysteine with potential metal-chelating properties; these garlic constituents may also protect from metal-catalyzed oxidative damage. Rats fed garlic as 7% of their diet (either a week before, after, or during exposure to heavy metal toxins) for six weeks demonstrated significantly reduced lead, cadmium, or mercury accumulation in their livers.¹⁶⁵ Garlic treatment also reduced the frequency of metal-related lesions in the livers of rats in the same study. Garlic may also increase the bioaccessibility of iron and zinc (both antagonists of cadmium and lead absorption) from dietary cereal grains.¹⁶⁶ In a study of 117 car battery industry workers with occupational lead poisoning, garlic (1,200 mg dried powder) daily for four weeks lowered blood lead as effectively as D-penicillamine (by approximately 18%). Additionally, treatment with garlic showed less adverse effects and more clinical improvement as compared with D-penicillamine.¹⁶⁷

Cilantro

Cilantro (Coriandrum sativum) can bind and immobilize mercury and methylmercury from contaminated water.¹⁶⁸ In mouse models, cilantro suspensions significantly reduced the deposition of lead into bones and reduced microscopic signs of lead-induced kidney and testicular damage.^169,170 In a case report, a patient exposed to mercury during amalgam-based dental filling removal developed adverse effects, including abnormal electrocardiogram (ECG) readings, which reverted almost back to normal after the administration of 400 mg/day of cilantro extract prior to and after removal for 2–3 weeks. Mercury deposits were reported to be absent following treatment, although the details of the treatment and mercury analysis in this report are unclear.¹⁷¹

Alpha-Lipoic Acid and Glutathione

Sulfur-containing compounds can complex with heavy metals, and the sulfur antioxidants alpha-lipoic acid and glutathione have been demonstrated to chelate a number of metals in cell culture (mercury for glutathione; cadmium, lead, zinc, cobalt, nickel, iron, and copper for alpha-lipoic acid).¹⁷² In a rat model, alpha-lipoic acid and glutathione reduced some of the adverse changes in blood parameters, including drops in red blood cell number and size as well as reductions in hemoglobin concentration brought about by intoxication with lead, cadmium, or copper.¹⁷³ Alpha-lipoic acid and glutathione in a rat model both reduced cadmium-associated oxidative stress and improved the activity of the antioxidant enzyme catalase in kidney tissue.¹⁷⁴

N-Acetyl Cysteine

N-acetyl cysteine provides a source of sulfur for glutathione production and is effective at reducing oxidative stress due to heavy metal toxicity.¹³⁷ As a sulfur-containing amino acid, it possesses two potential binding sites for metals and is capable of binding and sequestering divalent copper (II), trivalent iron (III), lead, mercury, and cadmium ions.¹⁷⁵ Chronic exposure to toxic metals can decrease cysteine levels.¹⁷⁶ In animal models and cell culture experiments, N-acetyl cysteine enhanced renal excretion of lead (Pb IV), lowered concentrations of mercury, and protected against cadmium-induced liver cell damage.¹⁷⁵ Cysteine may also be useful as part of a complete protein (such as a whey protein), which provides additional essential amino acids that may block the entry of metals into nervous tissue.¹⁷⁶

Glycine

Glycine is a conditionally essential amino acid found in plant and animal proteins. Chemically, glycine is the simplest of all amino acids. It combines with many toxic substances and converts them to less harmful forms, which are then excreted from the body. Glycine is also involved in the body’s natural synthesis of glutathione,¹⁷⁷ which itself is an important detoxifier of heavy metals.¹⁷² In a study of “Stronger Neo-Minophagen C,” a Japanese drug containing glycine, glycyrrhizin, and cysteine, which is said to be protective against chronic cadmium toxicity, the authors concluded that the reported beneficial effects were due to glycine. Glycine appeared to reduce the oxidative stress of chronic cadmium toxicity.¹⁷⁸

Probiotics

Among their myriad functions, certain strains of probiotic bacteria may minimize toxin exposure by trapping and metabolizing xenobiotics or heavy metals. The probiotic bacterial strains Lactobacillus rhamnosus (LC705 and GG), L. plantarum (CCFM8661 and CCFM8610), and Bifidobacterium breve Bbi 99/E8 were all shown to bind both cadmium and lead in laboratory studies.^179,180 Binding was observed for both live and heat-killed cultures of LC705. However, the efficiency of heavy metal binding by probiotics may decrease when multiple strains are combined.¹⁸⁰ In mouse models, two different Lactobacillus plantarum strains reduced tissue accumulation of cadmium and lead and protected against oxidative stress.^181,182

Chlorella

Chlorella, a unicellular green algae with the ability to bind cadmium (in animal models) and zinc, copper, and lead (in vitro), has been used to detoxify wastewater of metal contaminants.^183-185 In preclinical studies, chlorella lowered the bioavailability and accelerated the excretion of methylmercury¹⁸⁵ as well as cadmium¹⁸⁶ and reduced lead-induced bone marrow toxicity.¹⁸⁷