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Manganese and ADHD: The Concept of Neurotoxicity by Lawrence D. Rosen, MD

Environmental_HazardManganese (Mn) is a naturally occurring metallic element throughout the earth’s crust, found naturally in water, air and soil ( Mn is also found in foods and botanical products, and it is an essential trace element for human health.

While Mn deficiency can result in a multitude of health problems, it is currently Mn toxicity that is the focus of recent study in children’s environmental health.

Mn overexposure, either acute or chronic, has been mostly associated with neurotoxicity ( Historically, concern has centered on airborne exposure, though recently, drinking water exposures have been linked to childhood neurodevelopmental disorders. Publication of the article “Hair Manganese and Hyperactive Behaviors: Pilot Study of School-Age Children Exposed Through Tap Water” (Bouchard et al, Environ Health Perspect 115: 122-127, 2007) provides an opportunity to discuss the concept of environmental neurotoxicity.

The toxic effect of Mn is thought to be exerted via dose-dependent alteration of neurotransmitters (dopamine, GABA, serotonin), resulting in clinical symptoms such as motor and cognitive dysfunction. One such syndrome linked to Mn toxicity is Attention Deficit Hyperactivity Disorder (ADHD), a spectrum of clinically observable symptoms including distractibility, inattention, and restlessness (http://www.cdc.gove/ncbddd/adhd).

ADHD has increased in prevalence over the past several years, leading many to look for environmental factors potentially responsible for this rise. Mn has been implicated in various case reports ranging from Bangladesh to Boston (1,2). These cases all point toward contamination by naturally occurring Mn in drinking water sources. Well water seems to be the most common source, and clinical symptoms included all core features of ADHD noted above, leading to observable deficits in cognitive functioning. Bouchard et al studied 46 Canadian children in Quebec, 24 boys and 22 girls, aged 6-15, all of whom drank water from one of two well sources. Children whose homes were supplied by the well with higher Mn were more likely to suffer from ADHD symptoms based on parent and teacher ratings, and level of hair Mn elevation was significantly correlated with level of cognitive and behavioral disturbance.

What general lessons can we learn from this study?

Chronic low level excessive exposure of metallic elements, including Mn, can lead to neurotoxicity in children. Other such elements implicated in the development of ADHD include lead and mercury (3,4). Furthermore, multiple chronic exposures may be worse than one acute exposure. And mineral deficiencies (e.g. iron and zinc) may contribute to symptomatology in the face of metal toxicities (5,6). We need to study this concept more thoroughly, as millions of children across the world are at risk.

How we best measure metal toxicity is up for debate. Hair tests have been criticized, as have blood and urine measurements. We need better standards for what constitutes a safe level (probably zero is optimal) and how best to measure these levels.

There is certainly individuality in ability to excrete metallic toxins, and this genomic-metabolomic individuality may explain why some children exhibit clinical signs of neurotoxicity while others seem “unharmed.” Can we identify those at highest risk? Can we intervene before we see clinical symptoms?

Prevention of exposure is, of course, the ideal way to avoid neurotoxicity. Even prenatal exposure to Mn has been linked to childhood behavioral disturbances (7). While we are working on limiting industrial sources and cleaning up natural sources of Mn and other potentially toxic metallic elements, how do we treat those children with existing toxicity? We need to identify safe and effective methods of increasing excretion of toxins while not eliminating essential minerals at the same time.

Print References:
Wasserman GA, et al: Water manganese exposure and children’s intellectual function in Araihazar, Bangladesh. Environ Health Perspect 114: 124-129, 2006.

Woolf A, et al: A child with chronic manganese exposure from drinking water. Environ Health Perspect 110: 613-616, 2002.

Braun JM, et al: Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114: 1904-1909, 2006.

Cheuk DK, Wong V: Attention-deficit hyperactivity disorder and blood mercury level: a case-control study in Chinese children. Neuropediatrics 37: 234-240, 2006.

Konofal E, et al: Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 158: 1113-1115, 2004.

Arnold LE, et al: Serum zinc correlates with parent- and teacher-rated inattention in children with attention-deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 15: 628-636, 2005. Neurotoxicol Tertol 29: 181-187, 2007.


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