Heavy Metal Detoxification
Common Heavy Metal Toxicants and Associated Health Risks
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 (Houston 2011). 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) (ATSDR 2001). 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 GI tract and are becoming a major source of mercury exposure in humans (Houston 2011). 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 (Nierenberg 1998; Bernhoft 2012).
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 (Houston 2011; Sällsten 2000; Houston 2011). Mercury, particularly when inhaled as mercury vapors, can distribute to many organs, but may concentrate in the brain and kidneys (ATSDR 2001). It can also cross the placenta and be found in breast milk (Yang 1997).
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 (Houston 2011). Mercury can also directly accelerate the oxidative destruction of cell membranes and LDL cholesterol particles as well as bind to and inactivate the cellular antioxidants N-acetyl cysteine, alpha-lipoic acid, and glutathione (Houston 2011). 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); GI tract (eg, nausea, diarrhea, ulceration); and kidneys (failure) (Houston 2011; ATSDR 2001). Mercury may also accumulate in the thyroid and increase the risk of autoimmune disorders (Gallagher 2012), and may cause contact dermatitis (Caravati 2008).
Lead toxicity is one of the most frequently reported unintentional toxic heavy metal exposures and the leading cause of single metal toxicity in children (Bronstein 2012). 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 (ATSDR 2008a; Rodrigues 2010). Animal models also suggest that lead can be absorbed through the skin; lead acetate can be found in some cosmetic products (ATSDR 2008a; ATSDR 2007b). Children absorb lead up to 8-times more efficiently than adults (Abelsohn 2010). Ingestion of deteriorating lead-based paint chips or dust is the primary source of lead exposure in children (CDC 2009; Manton 2000). Also, toys and other children’s products may contain lead or be painted with lead-based paint; imported children’s products pose greater risk (Rossiter 2013; EPA 2013; Lipton 2007; DOH 2007). 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) (CPSC 2013); 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 (ATSDR 2007b).
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) (Kirberger 2013). 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 (ATSDR 2007b).
Acute cadmium intoxication is a potentially fatal, but very rare event (Bronstein 2012); chronic exposure to cadmium presents a larger threat to human health (Thévenod 2013). 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 (Sigel 2013). Cadmium is excreted slowly and may remain in the body for more than 20-30 years (Sigel 2013; Thévenod 2013). As it mimics zinc, cadmium is thought to exert its toxic activity by disrupting zinc metabolism; there are about 3000 different enzymes and structural proteins in human metabolism that require zinc for their activity and are potential targets of cadmium toxicity (Sigel 2013). Cadmium interferes with the cellular balance of zinc, and nutritional zinc or iron deficiencies can increase cadmium absorption (Sigel 2013; Thévenod 2013). 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 (Sigel 2013; ATSDR 2012a; ATSDR 2012b; Thévenod 2013; Sinicropi 2010).
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 (ATSDR 2011). It is one of the more commonly reported sources of unintentional intoxications (Bronstein 2012). 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 (ATSDR 2007a). 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, GI tract, and spleen; it can also cross the placenta (Ibrahim, Froberg 2006). Some inorganic arsenic can be converted to organic arsenic compounds in the liver (monomethylarsonic and dimethylarsinic acids) that have less acute toxicity (Ibrahim, Froberg 2006; ATSDR 2007a). 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) (Ibrahim, Froberg 2006).
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 (Ibrahim, Froberg 2006). 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 (Rusyniak 2010; ATSDR 2007a). Organic forms of arsenic have little acute toxicity compared to inorganic arsenic and arsine gas, the other two chemical forms of arsenic, which are more toxic (Ibrahim, Froberg 2006). Chronic inorganic arsenic exposure can result in anemia, neuropathy, or liver toxicity within a few weeks to months (ATSDR 2004; Ibrahim, Froberg 2006). 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”) (Ibrahim, Froberg 2006; ATSDR 2007a). Chronic exposure to arsenic has been associated with several types of cancer (skin, lung, liver, bladder, and kidney) (Ibrahim, Froberg 2006). Chronic exposure to dimethylarsinic acid, a form of organic arsenic, may cause kidney damage (ATSDR 2007a).
There are several other metals with documented toxicities and varying risk of unintentional overexposure.
Iron. Iron toxicity is the most common metal toxicity worldwide (Crisponi 2013; Kontoghiorghes 2004). The classic symptom of iron overload, especially in the context of the disease hemochromatosis, is skin hyperpigmentation (to a bronze or grey 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 (Siddique 2012). 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 (Araujo 1995; Nelson 1995; Sahinbegovic 2010; Ellervik 2012; Kallianpur 2004; Dongiovanni 2011; Kremastinos 2011). 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 (Hewitt 1990; Crisponi 2013). 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 (Bronstein 2012). Elevated levels of aluminum in the brains of some Alzheimer’s patients is of unknown significance as to correlation and cause; data supporting the association is inconclusive, with more study required to determine if aluminum plays a causal role in Alzheimer’s disease pathogenesis (Becaria 2002; Lemire 2011; Percy 2011).
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’s disease) can be neurotoxic (Wright 2007), and acute unintentional copper toxicities are more frequently reported than those of arsenic (Bronstein 2012).
Miscellaneous. Acute manganese intoxication has also been infrequently reported to U.S. poison control centers (Bronstein 2012). 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 (Shelleh 2012).