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In nature, iron is usually found in its oxidized form, iron (III) oxide, which is insoluble. Ferrous iron, iron (II), is soluble and its toxicity varies, largely with the integrity of the gastrointestinal lining. Iron supplements are typically used to treat anemia. Modalities include: diet, parasite control, vitamin A, riboflavin (B), vitamin C (for absorption), folate(B), vitamin B and multivitamin-multimineral supplements, with or without iron; potentially avoiding the use of iron only supplements.
The amount of iron ingested may give a clue to potential toxicity. The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Toxic effects begin to occur at doses above 10–20 mg/kg of elemental iron. Ingestions of more than 50 mg/kg of elemental iron are associated with severe toxicity.
- A 325-mg tablet of ferrous sulfate heptahydrate has 65 mg (20%) of elemental iron
- A 325-mg tablet of ferrous gluconate has 39 mg (12%) of elemental iron
- A 325-mg tablet of ferrous fumarate has 107.25 mg (33%) of elemental iron
- 200 mg ferrous sulfate, dried, has 65 mg (33%) of elemental iron
In terms of blood values, iron levels above 350–500 µg/dL are considered toxic, and levels over 1000 µg/dL indicate severe iron poisoning.
In the United States, overdose exposure to all formulations of "vitamins" was reported by 62,562 individuals in 2004 (nearly 80% [~78%, n=48,989] of these exposures were in children under the age of 6), leading to 53 "major" life-threatening outcomes and 3 deaths (2 from vitamins D and E; 1 from polyvitaminic type formula, with iron and no fluoride). This may be compared to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). In 2010, 71,000 exposures to various vitamins and multivitamin-mineral formulations were reported to poison control centers, which resulted in 15 major reactions but no deaths.
Before 1998, several deaths per year were associated with pharmaceutical iron-containing supplements, especially brightly colored, sugar-coated, high-potency iron supplements, and most deaths were children. Unit packaging restrictions on supplements with more than 30 mg of iron have since reduced deaths to 0 or 1 per year. These statistics compare with 59 confirmed deaths due to aspirin poisoning in 2003 and 147 deaths known to be associated with acetaminophen-containing products in 2003.
With few exceptions, like some vitamins from B-complex, hypervitaminosis usually occurs more with fat-soluble vitamins (D, E, K and A or 'DEKA'), which are stored in the liver and fatty tissues of the body. These vitamins build up and remain for a longer time in the body than water-soluble vitamins.
Conditions include:
- Hypervitaminosis A
- Hypervitaminosis D
- Hypervitaminosis E
- Hypervitaminosis K, unique as the true upper limit is less clear as is its bioavailability.
According to Williams' Essentials of Diet and Nutrition Therapy it is difficult to set a DRI for vitamin K because part of the requirement can be met by intestinal bacterial synthesis.
- Reliable information is lacking as to the vitamin K content of many foods or its bioavailability. With this in mind the Expert Committee established an AI rather than an RDA.
- This RDA (AI for men age 19 and older is 120 µg/day, AI for women is 90 µg/day) is adequate to preserve blood clotting, but the correct intake needed for optimum bone health is unknown. Toxicity has not been reported.
High-dosage A; high-dosage, slow-release vitamin B; and very high-dosage vitamin B alone (i.e. without vitamin B complex) hypervitaminoses are sometimes associated with side effects that usually rapidly cease with supplement reduction or cessation.
High doses of mineral supplements can also lead to side effects and toxicity. Mineral-supplement poisoning does occur occasionally, most often due to excessive intake of iron-containing supplements.
Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans).
This led investigators to the discovery of a gene polymorphism in the gene for ferroportin, which predisposes some people of African descent to iron overload.
Individuals of sub-Saharan African descent with ferroportin Q248H are more likely to be diagnosed with African iron overload than individual without ferroportin mutation because individuals with ferroportin Q248H have elevated level of serum ferritin concentration. Individuals of African descent should also avoid drinking traditional beer.
Since lead has been used widely for centuries, the effects of exposure are worldwide. Environmental lead is ubiquitous, and everyone has some measurable blood lead level. Atmospheric lead pollution increased dramatically beginning in the 1950s as a result of the widespread use of leaded gasoline. Lead is one of the largest environmental medicine problems in terms of numbers of people exposed and the public health toll it takes. Lead exposure accounts for about 0.2% of all deaths and 0.6% of disability adjusted life years globally.
Although regulation reducing lead in products has greatly reduced exposure in the developed world since the 1970s, lead is still allowed in products in many developing countries. In all countries that have banned leaded gasoline, average blood lead levels have fallen sharply. However, some developing countries still allow leaded gasoline, which is the primary source of lead exposure in most developing countries. Beyond exposure from gasoline, the frequent use of pesticides in developing countries adds a risk of lead exposure and subsequent poisoning. Poor children in developing countries are at especially high risk for lead poisoning. Of North American children, 7% have blood lead levels above 10 μg/dL, whereas among Central and South American children, the percentage is 33 to 34%. About one fifth of the world's disease burden from lead poisoning occurs in the Western Pacific, and another fifth is in Southeast Asia.
In developed countries, people with low levels of education living in poorer areas are most at risk for elevated lead. In the US, the groups most at risk for lead exposure are the impoverished, city-dwellers, and immigrants. African-American children and those living in old housing have also been found to be at elevated risk for high blood lead levels in the US. Low-income people often live in old housing with lead paint, which may begin to peel, exposing residents to high levels of lead-containing dust.
Risk factors for elevated lead exposure include alcohol consumption and smoking (possibly because of contamination of tobacco leaves with lead-containing pesticides). Adults with certain risk factors might be more susceptible to toxicity; these include calcium and iron deficiencies, old age, disease of organs targeted by lead (e.g. the brain, the kidneys), and possibly genetic susceptibility.
Differences in vulnerability to lead-induced neurological damage between males and females have also been found, but some studies have found males to be at greater risk, while others have found females to be.
In adults, blood lead levels steadily increase with increasing age. In adults of all ages, men have higher blood lead levels than women do. Children are more sensitive to elevated blood lead levels than adults are. Children may also have a higher intake of lead than adults; they breathe faster and may be more likely to have contact with and ingest soil. Children of ages one to three tend to have the highest blood lead levels, possibly because at that age they begin to walk and explore their environment, and they use their mouths in their exploration. Blood levels usually peak at about 18–24 months old. In many countries including the US, household paint and dust are the major route of exposure in children.
Evidence suggests lead exposure is associated with high blood pressure, and studies have also found connections between lead exposure and coronary heart disease, heart rate variability, and death from stroke, but this evidence is more limited. People who have been exposed to higher concentrations of lead may be at a higher risk for cardiac autonomic dysfunction on days when ozone and fine particles are higher.
Estrogen birth control pills may increase the amount of copper in humans, but was not shown to increase absorption. Copper Intrauterine devices (IUDs) have been questioned anecdotally, with people claiming copper toxicity, but there is currently no scientific evidence to substantiate this claim. Estrogen increases the absorption of copper, making women more likely to carry excess copper even when no birth control is used.
The amount of estrogen (or copper) contained in these modern forms of contraception are generally considered safe, and the former restrictions for estrogen use (not to be used by women older than 40, 35 for smokers) were lifted in 1989.
There are conditions in which an individual's copper metabolism is compromised to such an extent that birth control may cause an issue with copper accumulation. They include toxicity or just increased copper from other sources, as well as the increased copper level of the individual's mother via the placenta before birth. The two hormones commonly used in birth control, estrogen and progestin, protect from each other's complications, so a combination method may work best. At least when existing imbalances have been treated.
Mild iron deficiency can be prevented or corrected by eating iron-rich foods and by cooking in an iron skillet. Because iron is a requirement for most plants and animals, a wide range of foods provide iron. Good sources of dietary iron have heme-iron, as this is most easily absorbed and is not inhibited by medication or other dietary components. Three examples are red meat, poultry, and insects. Non-heme sources do contain iron, though it has reduced bioavailability. Examples are lentils, beans, leafy vegetables, pistachios, tofu, fortified bread, and fortified breakfast cereals.
Iron from different foods is absorbed and processed differently by the body; for instance, iron in meat (heme-iron source) is more easily absorbed than iron in grains and vegetables ("non-heme" iron sources). Minerals and chemicals in one type of food may also inhibit absorption of iron from another type of food eaten at the same time. For example, oxalates and phytic acid form insoluble complexes which bind iron in the gut before it can be absorbed.
Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, vegetarians and vegans should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry. Legumes and dark-green leafy vegetables like broccoli, kale and oriental greens are especially good sources of iron for vegetarians and vegans. However, spinach and Swiss chard contain oxalates which bind iron, making it almost entirely unavailable for absorption. Iron from non-heme sources is more readily absorbed if consumed with foods that contain either heme-bound iron or vitamin C. This is due to a hypothesised "meat factor" which enhances iron absorption.
Following are two tables showing the richest foods in heme and non-heme iron.
In both tables, food serving sizes may differ from the usual 100g quantity for relevancy reasons. Arbitrarily, the guideline is set at 18 mg, which is the USDA Recommended Dietary Allowance for women aged between 19 and 50.
Iron deficiency can have serious health consequences that diet may not be able to quickly correct; hence, an iron supplement is often necessary if the iron deficiency has become symptomatic.
Iron is needed for bacterial growth making its bioavailability an important factor in controlling infection. Blood plasma as a result carries iron tightly bound to transferrin, which is taken up by cells by endocytosing transferrin, thus preventing its access to bacteria. Between 15 and 20 percent of the protein content in human milk consists of lactoferrin that binds iron. As a comparison, in cow's milk, this is only 2 percent. As a result, breast fed babies have fewer infections. Lactoferrin is also concentrated in tears, saliva and at wounds to bind iron to limit bacterial growth. Egg white contains 12% conalbumin to withhold it from bacteria that get through the egg shell (for this reason, prior to antibiotics, egg white was used to treat infections).
To reduce bacterial growth, plasma concentrations of iron are lowered in a variety of systemic inflammatory states due to increased production of hepcidin which is mainly released by the liver in response to increased production of pro-inflammatory cytokines such as Interleukin-6. This functional iron deficiency will resolve once the source of inflammation is rectified; however, if not resolved, it can progress to Anaemia of Chronic Inflammation. The underlying inflammation can be caused by fever, inflammatory bowel disease, infections, Chronic Heart Failure (CHF), carcinomas, or following surgery.
Reflecting this link between iron bioavailability and bacterial growth, the taking of oral iron supplements in excess of 200 mg/day causes a relative overabundance of iron that can alter the types of bacteria that are present within the gut. There have been concerns regarding parenteral iron being administered whilst bacteremia is present, although this has not been borne out in clinical practice. A moderate iron deficiency, in contrast, can provide protection against acute infection, especially against organisms that reside within hepatocytes and macrophages, such as malaria and tuberculosis. This is mainly beneficial in regions with a high prevalence of these diseases and where standard treatment is unavailable.
Even though zinc is an essential requirement for a healthy body, excess zinc can be harmful, and cause zinc toxicity. Such toxicity levels have been seen to occur at ingestion of greater than 225 mg of Zinc. Excessive absorption of zinc can suppress copper and iron absorption. The free zinc ion in solution is highly toxic to bacteria, plants, invertebrates, and even vertebrate fish.
One manifestation of copper toxicity, cirrhosis of the liver in children (Indian childhood cirrhosis), has been linked to boiling milk in copper cookware. The Merck Manual states recent studies suggest that a genetic defect is associated with this particular cirrhosis.
It is difficult to differentiate the effects of low level metal poisoning from the environment with other kinds of environmental harms, including nonmetal pollution. Generally, increased exposure to heavy metals in the environment increases risk of developing cancer.
Without a diagnosis of metal toxicity and outside of evidence-based medicine, but perhaps because of worry about metal toxicity, some people seek chelation therapy to treat autism, cardiovascular disease, Alzheimer's disease, or any sort of neurodegeneration. Chelation therapy does not improve outcomes for those diseases.
Chronic arsenic poisoning results from drinking contaminated well water over a long period of time. Many aquifers contain high concentration of arsenic salts. The World Health Organization (WHO) recommends a limit of 0.01 mg/L (10 parts per billion) of arsenic in drinking water. This recommendation was established based on the limit of detection for most laboratories' testing equipment at the time of publication of the WHO water quality guidelines. More recent findings show that consumption of water with levels as low as 0.00017 mg/L (0.17 parts per billion) over long periods of time can lead to arsenicosis.
From a 1988 study in China, the US protection agency quantified the lifetime exposure of arsenic in drinking water at concentrations of 0.0017 mg/L, 0.00017 mg/L, and 0.000017 mg/L are associated with a lifetime skin cancer risk of 1 in 10,000, 1 in 100,000, and 1 in 1,000,000 respectively. WHO asserts that a level of 0.01 mg/L poses a risk of 6 in 10000 chance of lifetime skin cancer risk and contends that this level of risk is acceptable.
One of the worst incidents of arsenic poisoning via well water occurred in Bangladesh, which the World Health Organization called the "largest mass poisoning of a population in history."
Mining techniques such as hydraulic fracturing may mobilize arsenic in groundwater and aquifers due to enhanced methane transport and resulting changes in redox conditions, and inject fluid containing additional arsenic.
Iron deficiency can be avoided by choosing appropriate soil for the growing conditions (e.g., avoid growing acid loving plants on lime soils), or by adding well-rotted manure or compost. If iron deficit chlorosis is suspected then check the pH of the soil with an appropriate test kit or instrument. Take a soil sample at surface and at depth. If the pH is over seven then consider soil remediation that will lower the pH toward the 6.5 - 7 range. Remediation includes: i) adding compost, manure, peat or similar organic matter (warning. Some retail blends of manure and compost have pH in the range 7 - 8 because of added lime. Read the MSDS if available. Beware of herbicide residues in manure. Source manure from a certified organic source.) ii) applying Ammonium Sulphate as a Nitrogen fertilizer (acidifying fertilizer due to decomposition of ammonium ion to nitrate in the soil and root zone) iii) applying elemental Sulphur to the soil (oxidizes over the course of months to produce sulphate/sulphite and lower pH). Note: adding acid directly e.g. sulphuric/hydrochloric/citric acid is dangerous as you may mobilize metal ions in the soil that are toxic and otherwise bound. Iron can be made available immediately to the plant by the use of iron sulphate or iron chelate compounds. Two common iron chelates are Fe EDTA and Fe EDDHA. Iron sulphate (Iron(II)_sulfate) and iron EDTA are only useful in soil up to PH 7.1 but they can be used as a foliar spray (Foliar_feeding). Iron EDDHA is useful up to PH 9 (highly alkaline) but must be applied to the soil and in the evening to avoid photodegradation. EDTA in the soil may mobilize Lead, EDDHA does not appear to.
Organic arsenic is less harmful than inorganic arsenic. Seafood is a common source of the less toxic organic arsenic in the form of arsenobetaine. The arsenic reported in 2012 in fruit juice and rice by "Consumer Reports" was primarily inorganic arsenic.
Some of the toxic effects of mercury are partially or wholly reversible, either through specific therapy or through natural elimination of the metal after exposure has been discontinued. Autopsy findings point to a half-life of inorganic mercury in human brains of 27.4 years. Heavy or prolonged exposure can do irreversible damage, in particular in fetuses, infants, and young children. Young's syndrome is believed to be a long-term consequence of early childhood mercury poisoning.
Mercuric chloride may cause cancer as it has caused increases in several types of tumors in rats and mice, while methyl mercury has caused kidney tumors in male rats. The EPA has classified mercuric chloride and methyl mercury as possible human carcinogens (ATSDR, EPA)
Manganism has become an active issue in workplace safety as it has been the subject of numerous product liability lawsuits against manufacturers of arc welding supplies. In these lawsuits, welders have accused the manufacturers of failing to provide adequate warning that their products could cause welding fumes to contain dangerously high manganese concentrations that could lead welders to develop manganism. Companies employing welders are also being sued, for what colloquially is known as "welders' disease." However, studies fail to show any link between employment as a welder and manganism (or other neurological problems).
Manganism is also documented in reports of illicit methcathinone manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.
Reports also mention such sources as contaminated drinking water, and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT), which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust, and manganese ethylene-bis-dithiocarbamate (Maneb), a pesticide.
Cows and horses as well as pet animals are also susceptible to the effects of lead toxicity. Sources of lead exposure in pets can be the same as those that present health threats to humans sharing the environment, such as paint and blinds, and there is sometimes lead in toys made for pets. Lead poisoning in a pet dog may indicate that children in the same household are at increased risk for elevated lead levels.
The Red River Delta near Hanoi has high levels of manganese or arsenic in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium, and barium.
It is most common in certain European populations (such as the Irish and Norwegians) and occurs in 0.6% of the population. Men with the disease are 24 times more likely to experience symptoms than affected women.
Siderosis is the deposition of iron in tissue.
When used without qualification, it usually refers to an environmental disease of the lung.
Also Siderosis Bulbi, deposition of iron into the eye causing injury as the material chemically reacts with tissues and cells.
Affected individuals over age 40 or who have high serum ferritin levels are at risk for developing cirrhosis. Iron overload increases the risk of hepatocellular carcinoma. This risk is greater in those with cirrhosis but is still present in those without cirrhosis. Significant problems occur in around one in ten.
Mercury poisoning can be prevented or minimized by eliminating or reducing exposure to mercury and mercury compounds. To that end, many governments and private groups have made efforts to heavily regulate the use of mercury, or to issue advisories about its use.
For example, the export from the European Union of mercury and some mercury compounds has been prohibited since 15 March, 2010.
The United States Environmental Protection Agency (EPA) issued recommendations in 2004 regarding exposure to mercury in fish and shellfish. The EPA also developed the "Fish Kids" awareness campaign for children and young adults on account of the greater impact of mercury exposure to that population.