James Greenblatt, MD
Every day we are exposed to toxins from our environment. We may ingest lead and copper from drinking water, phosphate from processed food and soda, various synthetic chemicals from plastic food containers, and pesticides from fruits and vegetables. Both natural heavy metals and man-made chemicals disrupt hormones and brain development. The brain, especially the developing brain, is very vulnerable to contaminants because of its large size (relative to total body weight) and its high concentration of fats which serve as a reservoir for toxicants to build up. This article will explain the role that heavy metals and environmental toxins play in ADHD.
In January 2016, President Obama declared a state of emergency in Flint, Michigan where thousands of residents were exposed to high levels of lead in their drinking water. The corrosive water from the Flint River caused lead from old water pipes to leach into the water supply, putting up to 12,000 children at risk of consuming dangerous levels of lead. Lead poisoning can cause irreversible brain damage and even death, and growing children are especially susceptible to its poisonous effects. Even low blood lead levels reduce IQ, the ability to pay attention, motor function, and academic achievement.
Blood lead levels in children have plummeted since the US phased out the use of leaded gas and paint in the 1970’s. Still, 24 million homes in the US contain deteriorated lead paint and elevated levels of lead-contaminated dust. Soil contains lead from air that settled during our previous industrial use. Old toys and toys from China may contain lead-based paint as well. Again, children are especially at risk of lead poisoning in these environments because they are likely to put their contaminated toys or hands in their mouth.
Since lead poisoning causes cognitive, motor, and behavioral changes, it is not surprising that it also causes ADHD. Lead exposure is estimated to account for 290,000 excess cases of ADHD in US children (Braun et al., 2006). A study on 270 mother-child pairs in Belgium found that doubling prenatal lead exposure (measured in cord blood) was associated with a more than three times higher risk for hyperactivity in boys and girls at age 7-8 (Sioen et al., 2013). A larger study on almost 5,000 US children aged 4-15 found children with the highest blood lead levels were over four times as likely to have ADHD as children with the lowest blood lead levels (Braun et al., 2006).
MRI scans from participants of the Cincinnati Lead Study had striking results: childhood lead exposure was associated with brain volume loss in adulthood. Individuals with higher blood lead levels as children had less gray matter in some brain areas. The main brain region affected was the prefrontal cortex which is responsible for executive function, behavioral regulation, and fine motor control (Cecil et al., 2008).
The CDC has set a blood lead level of 5 µg/dL as the reference value to identify children who require case management. However, many studies have shown lead levels <5 μg/dL still pose problems. For instance, researchers assessing 256 children aged 8-10 concluded, “even low blood lead levels (<5 μg/dL) are associated with inattentive and hyperactivity symptoms and learning difficulties in school-aged children” (Kim et al., 2010).
Copper is an essential trace mineral we must consume from our food supply. It is found in oysters and other shellfish, whole grains, beans, nuts, and potatoes. Like lead, copper can leach into the water supply when copper pipes corrode. One of copper’s roles in the body is to help produce dopamine, the neurotransmitter that provides alertness. However, too much copper creates an excess of dopamine leading to an excess of the neurotransmitter norepinephrine. High levels of these neurotransmitters lead to symptoms similar to ADHD symptoms: hyperactivity, impulsivity, agitation, irritability, and aggressiveness. In children with excess copper, stimulant medications don’t work as well and tend to cause side effects (agitation, anxiousness, change in sleep and appetite). Most ADHD medications work by increasing levels of dopamine, intensifying the effects of excess copper. In addition, excess copper blocks the production of serotonin, a mood-balancing neurotransmitter. This triggers emotional, mental, and behavioral problems, from depression and anxiety to paranoia and psychosis.
The neurotoxic effects of excess copper are well known and a few studies have assessed copper’s role in ADHD symptoms. When researchers compared copper levels in 58 ADHD children to levels in 50 control children, they observed that copper levels were higher in ADHD children. ADHD children also had a higher copper-to-zinc ratio that positively correlated with teacher-rated inattention (Viktorinova et al., 2016). Researchers in Belgium measured the heavy metal exposure of 600 adolescents aged 13-17. They found that an increase in blood copper was associated with a decrease in sustained attention and a decrease in short-term memory. This held true even though this population had normal copper levels (Kicinski et al., 2015). In a randomized controlled trial on 80 adults with ADHD, lower baseline copper levels were associated with better response to treatment with a vitamin-mineral supplement. Among those in the highest copper tertile, only 35% were responders compared to 77% in the middle copper tertile (Rucklidge et al., 2014).
Phosphate is a charged particle (an electrolyte) that contains phosphorus. Phosphorus is the second most abundant mineral in the body (the first is calcium). Phosphorus is a building block for bones and about 85% of total body phosphorus is found in the bones. Deficiencies are rare because phosphorus is naturally abundant in protein-rich foods like meat, poultry, fish, eggs, milk, and milk products as well as in nuts, legumes, cereals, and grains. Although phosphorus is an essential nutrient, too much can be problematic. The phosphate content of processed foods is much higher than that of natural foods, because phosphates are commonly used as additives and preservatives in food production. Our daily intake of phosphate food additives has more than doubled since the 1990’s (Ritz et al., 2012). Phosphorus, especially the form found in processed meats, canned fish, baked goods, and soda is quickly absorbed into the bloodstream so levels can rise rapidly.
Phosphorus reduces the absorption of other vital nutrients, many of which ADHD children are deficient in to begin with. For instance, too much phosphorus can lower calcium levels. High phosphorus coupled with low calcium intake leads to poor bone health. The typical American diet contains two to four times more phosphorus than calcium and soda is often a major contributor to this imbalance. In the body, phosphorus and magnesium bind together, making both minerals unavailable for absorption. This is most apparent when magnesium consumption is low and intake of phosphorus is high. Researchers have found that adding Pepsi to men’s diet for two consecutive days causes their blood phosphate levels to increase and their magnesium excretion to decrease (Weiss et al., 1992).
In the 1990’s, German pharmacist Hertha Hafer discovered that excess dietary phosphate triggered her son’s ADHD symptoms. Within her book, The Hidden Drug, Dietary Phosphate: Cause of Behavior Problems, Learning Difficulties and Juvenile Delinquency, she presents a low phosphate diet as a treatment for ADHD. A low phosphate diet led to dramatic improvements in her son’s behavior, well-being, and school performance, rendering medication unnecessary. Her family’s ADHD problem was resolved and her son had no further problems as long as he avoided high phosphate foods. Hafer finds that children with mild ADHD can improve simply by removing processed meats and phosphate-containing beverages like soda and sports drinks from their diets (Waterhouse, 2008).
Everyday plastic products contain hormone-disrupting chemicals, such as Bisphenol A (BPA) and phthalates, that can migrate into our body and affect the brain and nervous system. These environmental toxins bind to zinc and deplete zinc levels in the body. Phthalates are synthetic chemicals used to make plastics soft and flexible. Phthalates are used in hundreds of consumer products and humans are exposed to them daily though air, water, and food. Di(2-ethylhexyl) phthalate (DEHP) is the name for the most common phthalate. It can be found in products made with plastic such as tablecloths, floor tiles, shower curtains, garden hoses, swimming pool liners, raincoats, shoes, and car upholstery. Based on animal studies, the Environmental Protection Agency (EPA) has classified DEHP as a “probable human carcinogen.” Such studies have shown that DEHP exposure affects development and reproduction.
Multiple studies have linked phthalates with ADHD. Researchers assessed the urine phthalate concentrations and ADHD symptoms in 261 children aged 8-11. ADHD symptoms (inattention and hyperactivity/impulsivity), rated by the children’s teachers, were significantly associated with DEHP metabolites (breakdown products) (Kim et al., 2009).
Prenatal phthalate exposure is associated with problems in childhood behavior and executive functioning. Third-trimester urines from 188 pregnant women were collected and analyzed for phthalate metabolites. Their children were assessed for cognitive and behavioral development between the ages of 4 and 9. Phthalate metabolites were associated with worse aggression, conduct problems, attention problems, depression, externalizing problems, and emotional control (Engel et al., 2010).
Exposure to DEHP in pediatric intensive care units (PICU) is associated with attention deficits in children. In the hospital, DEHP can be found in and can leach from medical devices such as catheters, blood bags, breathing tubes, and feeding tubes. Researchers in Belgium measured levels of DEHP byproducts in the blood of 449 children aged 0-16 while they were staying in a pediatric intensive care unit. Four years later, the children’s neurocognitive development was tested and compared to that of healthy children. The researchers found that all medical devices inserted into the body actively leached DEHP. Predictably, hospitalized children had very high levels of DEHP byproducts throughout their stay in the intensive care unit. A high exposure to DEHP was strongly associated with attention deficit and impaired motor coordination four years after hospital admission. Phthalate exposure from the PICU explained half of the attention deficit in post-PICU patients (Verstraete et al., 2016).
BPA is another problem chemical which is found in food and drink packaging. Exposure to BPA may be related to behavior problems in children. A 2016 nationwide study of 460 children aged 8-15 found children with higher urinary levels of BPA had over five times higher odds of being diagnosed with ADHD (Tewar et al., 2016). In another study, researchers measured BPA concentration in urine samples from women at 27 weeks of pregnancy then assessed the behavior of their children at age 6-10. There was a significant positive association in boys between prenatal BPA concentration and internalizing and externalizing behaviors, withdrawn/depressed behavior, somatic problems, and oppositional/defiant behaviors. Researchers speculated that BPA may have disrupted maternal thyroid or gonadal hormones which are critical to proper brain development (Evan et al., 2014).
In addition to heavy metals and plasticizers, pesticides can cause ADHD symptoms. The American Academy of Pediatrics notes, “Children encounter pesticides daily in air, food, dust, and soil. For many children, diet may be the most influential source. Studies link early-life exposure to organophosphate insecticides with reductions in IQ and abnormal behaviors associated with ADHD and autism” (Roberts & Karr, 2012).
Among pesticides, insecticides may be the most harmful to humans. Insecticides were first developed during World War II as nerve gases. They work by targeting and destroying acetylcholinesterase, an enzyme that controls the neurotransmitter acetylcholine which plays a role in attention, learning, and short-term memory. In one study of 307 children aged 4-9, researchers found that lower acetylcholinesterase activity in boys was linked to a four times greater risk of poor attention and executive function and a six times greater risk of memory and learning problems (Suarez-Lopez et al., 2013). Organophosphates (OPs) are a common type of insecticide that target the nervous system. Forty different types of organophosphates are in use in the United States.
Scientists in California studied 320 mothers and their children. They evaluated urinary levels of metabolites of OPs when the mothers were pregnant. Then when the children were 3- and 5- years old, they were evaluated for ADHD. At both time points, levels of prenatal OP metabolites were positively associated with attention problems and ADHD. Children with mothers who had the highest levels of the OP metabolites were five times more likely to develop ADHD (Marks et al., 2010).
Even organophosphate exposure at low levels common among US children may contribute to ADHD prevalence. Researchers at Harvard University studied more than 1,000 children aged 8-15 from the general population and found that those with detectable urinary levels of an OP metabolite were nearly twice as likely to be diagnosed with ADHD (Bouchard et al., 2010).
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