15 replies to this topic

[Jacovis]

Well as can be seen from the studies below, LOW Iron may cause more severe ADHD symptoms for children with the disorder. Now my question is could LOW IRON also be a factor in Adult ADHD for some people, even men (for whom the concern healthwise is very much about not having TOO MUCH Iron)?

1: Child Psychiatry Hum Dev. 2007 Dec 29 [Epub ahead of print] Links
Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity.Oner P, Oner O.
Child Psychiatry Department, Ataturk Hospital, Ankara, Turkey.

Our aim was to investigate the relation between behavioral symptoms and hematological variables which are related with iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and reticulosite distribution width (RDW) in children and adolescents with pure Attention Deficit Hyperactivity Disorder (ADHD) or ADHD comorbid with other psychiatric disorders. The sample consisted of 151 subjects with ADHD, 45 of these subjects had other comorbid conditions. Conners Parent (CPRS) and Teacher Rating Scales (CTRS) were obtained. Comorbid ADHD subjects had lower mean hemoglogin and MCV. In the ADHD group in general, CPRS and CTRS Total scores were significantly negatively correlated with ferritin level. When only pure ADHD subjects were taken into account, the correlations did not reach statistical signifance. Overall, these results suggested that lower ferritin level was associated with higher behavioral problems reported by both parents and teachers. Presence of comorbid conditions might increase the effect of lower iron stores on behavioral measures.

PMID: 18165896 [PubMed - as supplied by publisher]


1: Med Hypotheses. 2007 Dec 26 [Epub ahead of print] Links
Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: The iron hypothesis.Cortese S, Lecendreux M, Bernardina BD, Mouren MC, Sbarbati A, Konofal E.
APHP, Child and Adolescent Psychopathology Unit, Robert Debré Hospital, Paris VII University, Paris, France; Child Neuropsychiatry Unit, G.B. Rossi Hospital, Department of Mother–Child and Biology-Genetics, Verona University, Verona, Italy.

Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.

PMID: 18164140 [PubMed - as supplied by publisher]


1: Pediatr Neurol. 2008 Jan;38(1):20-6. Links
Effects of iron supplementation on attention deficit hyperactivity disorder in children.Konofal E, Lecendreux M, Deron J, Marchand M, Cortese S, Zaïm M, Mouren MC, Arnulf I.
Hôpital Robert Debré, Service de Psychopathologie de l'Enfant et de l'Adolescent, Paris, France. eric.konofal@rdb.aphp.fr

Iron deficiency has been suggested as a possible contributing cause of attention deficit hyperactivity disorder (ADHD) in children. This present study examined the effects of iron supplementation on ADHD in children. Twenty-three nonanemic children (aged 5-8 years) with serum ferritin levels <30 ng/mL who met DSM-IV criteria for ADHD were randomized (3:1 ratio) to either oral iron (ferrous sulfate, 80 mg/day, n = 18) or placebo (n = 5) for 12 weeks. There was a progressive significant decrease in the ADHD Rating Scale after 12 weeks on iron (-11.0 +/- 13.9; P < 0.008), but not on placebo (3.0 +/- 5.7; P = 0.308). Improvement on Conners' Parent Rating Scale (P = 0.055) and Conners' Teacher Rating Scale (P = 0.076) with iron supplementation therapy failed to reach significance. The mean Clinical Global Impression-Severity significantly decreased at 12 weeks (P < 0.01) with iron, without change in the placebo group. Iron supplementation (80 mg/day) appeared to improve ADHD symptoms in children with low serum ferritin levels suggesting a need for future investigations with larger controlled trials. Iron therapy was well tolerated and effectiveness is comparable to stimulants.

PMID: 18054688 [PubMed - in process]


1: Tohoku J Exp Med. 2007 Nov;213(3):269-76. Links
Association between low serum ferritin and restless legs syndrome in patients with attention deficit hyperactivity disorder.Oner P, Dirik EB, Taner Y, Caykoylu A, Anlar O.
Child and Adolescent Psychiatry Division, Ataturk Hospital, Ankara, Turkey. pinaryoner@yahoo.com

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive inattention and/or hyperactivity-impulsivity. It has been suggested that ADHD symptoms are associated with restless legs syndrome (RLS), which is a neurological condition that is defined by an irresistible urge to move the legs. Increasing evidence suggests iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD and with RLS. To further define the relationship between iron deficiency and RLS in children and adolescents with ADHD, we evaluated 87 ADHD subjects: 79 boys and 8 girls with age 9.3 +/- 2.5 years (6-16 years). Various psychopathologies and the severity of the ADHD symptoms and serum ferritin levels were assessed. Diagnosis of RLS was made according to the International RLS Group criteria. The patients were evaluated for the iron deficiency (ferritin < 12 ng/ml). RLS was found in 29 (33.3%) of the 87 ADHD subjects. Parent- and teacher-rated behavioral and emotional problems and the severity of ADHD symptoms were not significantly different between ADHD subjects with RLS and those without RLS (n = 58). The rate of iron deficiency was significantly higher in ADHD subjects with RLS (n = 6, 20.7%) when compared with ADHD subjects without RLS (n = 1, 1.7%, p = 0.005). Our results showed that depleted iron stores might increase the risk of having RLS in ADHD subjects. Iron deficiency, which is associated with both ADHD and RLS, seems to be an important modifying factor in the relationship between these two conditions.

PMID: 17984624 [PubMed - indexed for MEDLINE]


1: Sleep Med. 2007 Nov;8(7-8):711-5. Epub 2007 Jul 20. Links
Impact of restless legs syndrome and iron deficiency on attention-deficit/hyperactivity disorder in children.Konofal E, Cortese S, Marchand M, Mouren MC, Arnulf I, Lecendreux M.
Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France. eric.konofal@rdb.aphp.fr

OBJECTIVE: Increasing evidence suggests a significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and restless legs syndrome (RLS). Iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD plus RLS (ADHD+RLS). To date, the impact of iron deficiency, RLS and familial history of RLS on ADHD severity has been scarcely examined in children. These issues are addressed in the present study. METHODS: Serum ferritin levels, familial history of RLS (diagnosed using National Institutes of Health (NIH) criteria) and previous iron supplementation in infancy were assessed in 12 ADHD+RLS children, 10 ADHD children and 10 controls. RLS was diagnosed using NIH-specific pediatric criteria, and ADHD severity was assessed using the Conners' Parent Rating scale. RESULTS: ADHD symptom severity was higher, although not significantly, in children with ADHD+RLS compared to ADHD. The mean serum ferritin levels were significantly lower in children with ADHD than in the control group (p<0.0005). There was a trend for lower ferritin levels in ADHD+RLS subjects versus ADHD. Both a positive family history of RLS and previous iron supplementation in infancy were associated with more severe ADHD scores. CONCLUSIONS: Children with ADHD and a positive family history of RLS appear to represent a subgroup particularly at risk for severe ADHD symptoms. Iron deficiency may contribute to the severity of symptoms. We suggest that clinicians consider assessing children with ADHD for RLS, a family history of RLS, and iron deficiency.

PMID: 17644481 [PubMed - in process]


1: Environ Health Perspect. 2007 Aug;115(8):A398-9; author reply A399. Links
Comment on:
Environ Health Perspect. 2006 Dec;114(12):1904-9.
Lead and neuroprotection by iron in ADHD.Konofal E, Cortese S.
PMID: 17687422 [PubMed - indexed for MEDLINE]


1: Arch Pediatr Adolesc Med. 2004 Dec;158(12):1113-5. Links
Comment in:
Arch Pediatr Adolesc Med. 2005 Aug;159(8):788; author reply 788.
Iron deficiency in children with attention-deficit/hyperactivity disorder.Konofal E, Lecendreux M, Arnulf I, Mouren MC.
Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, Paris, France. eric.konofal@rdb.ap-hop-paris.fr

BACKGROUND: Iron deficiency causes abnormal dopaminergic neurotransmission and may contribute to the physiopathology of attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To evaluate iron deficiency in children with ADHD vs iron deficiency in an age- and sex-matched control group. DESIGN: Controlled group comparison study. SETTING: Child and Adolescent Psychopathology Department in European Pediatric Hospital, Paris, France. PATIENTS: Fifty-three children with ADHD aged 4 to 14 years (mean +/- SD, 9.2 +/- 2.2 years) and 27 controls (mean +/- SD, 9.5 +/- 2.8 years). MAIN OUTCOME MEASURES: Serum ferritin levels evaluating iron stores and Conners' Parent Rating Scale scores measuring severity of ADHD symptoms have been obtained. RESULTS: The mean serum ferritin levels were lower in the children with ADHD (mean +/- SD, 23 +/- 13 ng/mL) than in the controls (mean +/- SD, 44 +/- 22 ng/mL; P < .001). Serum ferritin levels were abnormal (<30 ng/mL) in 84% of children with ADHD and 18% of controls (P < .001). In addition, low serum ferritin levels were correlated with more severe general ADHD symptoms measured with Conners' Parent Rating Scale (Pearson correlation coefficient, r = -0.34; P < .02) and greater cognitive deficits (r = -0.38; P < .01). CONCLUSIONS: These results suggest that low iron stores contribute to ADHD and that ADHD children may benefit from iron supplementation.

PMID: 15583094 [PubMed - indexed for MEDLINE]

[Jacovis]

Below are some studies, while not mentioning ADHD, which show that in women at least, even Iron deficiency alone (without actual Iron deficiency anemia) may be enough to reduce cognitive performance...


1: Am J Clin Nutr. 2007 Mar;85(3):778-87. Links
Iron treatment normalizes cognitive functioning in young women.Murray-Kolb LE, Beard JL.
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA. lmurrayk@jhsph.edu

BACKGROUND: Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning. Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency. OBJECTIVE: We aimed to examine the relation between iron status and cognitive abilities in young women. DESIGN: A blinded, placebo-controlled, stratified intervention study was conducted in women aged 18-35 y of varied iron status who were randomly assigned to receive iron supplements or a placebo. Cognition was assessed by using 8 cognitive performance tasks (from Detterman's Cognitive Abilities Test) at baseline (n = 149) and after 16 wk of treatment (n = 113). RESULTS: At baseline, the iron-sufficient women (n = 42) performed better on cognitive tasks (P = 0.011) and completed them faster (P = 0.038) than did the women with iron deficiency anemia (n = 34). Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women (n = 73) were intermediate between the 2 extremes of iron status. After treatment, a significant improvement in serum ferritin was associated with a 5-7-fold improvement in cognitive performance, whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks. CONCLUSIONS: Iron status is a significant factor in cognitive performance in women of reproductive age. Severity of anemia primarily affects processing speed, and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks. Thus, the effects of iron deficiency on cognition are not limited to the developing brain.

PMID: 17344500 [PubMed - indexed for MEDLINE]


http://www.eurekaler...s-mid040404.php
Moderate iron deficiency affects cognitive performance - but iron supplementation improves it
Young women who took iron supplementation for 16 weeks significantly improved their attention, short-term and long-term memory, and their performance on cognitive tasks, even though many were not considered to be anemic when the study began, according to researchers at Pennsylvania State University.
The study, the first to systematically examine the impact of iron supplementation on cognitive functioning in women aged 18 to 35 (average age 21), was presented at Experimental Biology 2004, in the American Society of Nutritional Sciences' scientific program. Dr. Laura Murray-Kolb, a postdoctoral fellow in the lab of Dr. John Beard, says the study shows that even modest levels of iron deficiency have a negative impact on cognitive functioning in young women. She says the study also is the first to demonstrate how iron supplementation can reverse this impact in this age group.

Baseline cognition testing, looking at memory, stimulus encoding, retrieval, and other measures of cognition, was performed on 149 women who classified as either iron sufficient, iron deficient but not anemic, or anemic. All of the women underwent a health history, and the research design controlled or took into account any differences in smoking, social status, grade point average, and other measures. The women were then given either 60 mg. iron supplementation (elemental iron) or placebo treatment for four months. At the end of that period, the 113 women remaining in the study took the same task again.

On the baseline test, women who were iron deficient but not anemic completed the tasks in the same amount of time as iron sufficient women of the same age, but they performed significantly worse. Women who were anemia also performed significantly worse, but in addition they took longer. The more anemic a woman was, the longer it took her to complete the tasks. However, supplementation and the subsequent increase in iron stores markedly improved cognition scores (memory, attention, and learning tasks) and time to complete the task.

This finding has great implications, says Dr. Murray-Kolb, because the prevalence of iron deficiency remains at 9 percent to 11 percent for women of reproductive age and 25 percent for pregnant women. In non-industrialized countries, the prevalence of anemia is over 40 percent in non-pregnant women and over 50 percent for pregnant women and for children aged five to 14. According to current prevalence estimates, iron deficiency affects the lives of more than two billion people worldwide.

The findings also are important, say the researchers, because they illustrate the significance of lower amounts of iron deficiency on cognitive functioning, including memory, attention, learning tasks, and time to complete studies.

Some of the known consequences of iron deficiency are reduced physical endurance, an impaired immune response, temperature regulation difficulties, changes in energy metabolism, and in children, a decrease in cognitive performance as well as negative affects on behavior. While iron deficiency was once presumed to exert most of its deleterious effects only if it had reached the level of anemia, it has more recently become recognized that many organs show negative changes in functioning before there is any drop in iron hemoglobin concentration.

Authors of the study are Dr. Murray-Kolb, Dr. Beard, both of the Nutritional Sciences Department at Penn State, and Dr. Keith Whitfield, of Penn State's Biobehavioral Health Department.

[stephen_b]

Here is a study with slightly different findings. They only found that low serum ferritin levels only correlated when kids' ADHD was "comorbid with other psychiatric disorders". Maybe there is some confounding going on?

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity (PMID: 18165896).

In the ADHD group in general, CPRS and CTRS Total scores were significantly negatively correlated with ferritin level. When only pure ADHD subjects were taken into account, the correlations did not reach statistical signifance.

Stephen

[Mind]

I suppose it might be a concern a few select people, however, most diets actually have way too much iron, enough to be detrimental to long term health (especially for older men).

[Jacovis]

The short article written below by Konofal and Cortese focus on the potential neuroprotective role of iron against the deleterious effect of lead on the development of ADHD symptoms...

http://www.pubmedcen...i?artid=1940080

Journal List > Environ Health Perspect > v.115(8); Aug 2007

PubMed articles by:
Konofal, E.
Cortese, S. Environ Health Perspect. 2007 August; 115(8): A398–A399.
doi: 10.1289/ehp.10304.
Copyright This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI
Perspectives
Correspondence
Lead and Neuroprotection by Iron in ADHD
Eric Konofal and Samuele Cortese
Child Psychopathology Unit, University Hospital Robert Debré, Paris, France, E-mail: eric.konofal@rdb.aphp.fr
The authors declare they have no competing financial interests.

We read with special interest the article by Braun et al. (2006). In this large survey, the authors concluded that prenatal exposure to tobacco and environmental lead are risk factors for attention deficit hyperactivity disorder (ADHD).
We would like to focus on the potential neuroprotective role of iron against the deleterious effect of lead on the development of ADHD symptoms.

Although the mechanisms underlying ADHD remain unclear, both genetic and environmental factors have been implicated. In a recent review on the implication of the dopaminergic system in the etiology of ADHD, Swanson et al. (2007) highlighted the importance of environmental risk factors as possible etiologies of dopamine deficit. Among these environmental factors, Swanson et al. (2007) cited the effects of lead exposure (at levels < 10 μg/dL) on ADHD-related behaviors and ADHD diagnosis.

Lead in the central nervous system may contribute to dopaminergic dysfunction inducing alteration of dopamine release and dopamine receptor density (Gedeon et al. 2001; Lidsky et al. 2003). Moreover, lead may disrupt the structure of the blood–brain barrier function essential for brain integrity (Dyatlov et al. 1998). Interestingly, Wang et al. (2007) recently reported that iron supplementation protects the integrity of the blood–brain barrier against lead insults. On the other hand, iron deficiency could increase the toxic effect of lead, suggesting a potent neuroprotective effect of iron supplementation on dopaminergic dysfunction due to lead exposure (Wright 1999; Wright et al. 2003)

In a controlled comparison group study, we (Konofal et al. 2004) showed that iron deficiency was correlated to ADHD symptoms severity, hypothesizing that iron supplementation may improve symptoms of ADHD in those subjects with low ferritin levels.

Given that lead exposure may contribute to ADHD and iron deficiency may exacerbate deleterious effects caused by lead, we recommend systematically seeking for iron deficiency in children with ADHD. We also think that controlled studies assessing the potential effectiveness of iron supplementation on ADHD symptoms should be encouraged. Such studies could aid the understanding of the complex pathophysiology underlying ADHD and provide effective therapeutic strategies for this disorder.

References
Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect. 2006;114:1904–1909. [PubMed]
Dyatlov VA, Platoshin AV, Lawrence DA, Carpenter DO. Lead potentiates cytokine- and glutamate-mediated increases in permeability of the blood-brain barrier. Neurotoxicology. 1998;19:283–291. [PubMed]
Gedeon Y, Ramesh GT, Wellman PJ, Jadhav AL. Changes in mesocorticolimbic dopamine and D1/D2 receptor levels after low level lead exposure: a time course study. Toxicol Lett. 2001;123(2–3):217–226. [PubMed]
Konofal E, Lecendreux M, Arnulf I, Mouren MC. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med. 2004;158(12):1113–1115. [PubMed]
Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain. 2003;126:5–19. [PubMed]
Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, et al. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev. 2007;17(1):39–59. [PubMed]
Wang Q, Luo W, Zheng W, Liu Y, Xu H, Zheng G, et al. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. Toxicol Appl Pharmacol. 2007;219(1):33–41. [PubMed]
Wright RO. The role of iron therapy in childhood plumbism. Curr Opin Pediatr. 1999;11(3):255–258. [PubMed]
Wright RO, Tsaih SW, Schwartz J, Wright RJ, Hu H. Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic. J Pediatrics. 2003;142(1):9–14.


1: Environ Health Perspect. 2006 Dec;114(12):1904-9. Links
Comment in:
Environ Health Perspect. 2007 Aug;115(8):A398-9; author reply A399.
Environ Health Perspect. 2007 Aug;115(8):A398; author reply A399.
Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP.
College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.

OBJECTIVE: The purpose of this study was to examine the association of exposures to tobacco smoke and environmental lead with attention deficit hyperactivity disorder (ADHD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Prenatal and postnatal tobacco exposure was based on parent report; lead exposure was measured using blood lead concentration. ADHD was defined as having current stimulant medication use and parent report of ADHD diagnosed by a doctor or health professional. RESULTS: Of 4,704 children 4-15 years of age, 4.2% were reported to have ADHD and stimulant medication use, equivalent to 1.8 million children in the United States. In multivariable analysis, prenatal tobacco exposure [odds ratio (OR) = 2.5; 95% confidence interval (CI), 1.2-5.2] and higher blood lead concentration (first vs. fifth quintile, OR = 4.1; 95% CI, 1.2-14.0) were significantly associated with ADHD. Postnatal tobacco smoke exposure was not associated with ADHD (OR = 0.6; 95% CI, 0.3-1.3; p = 0.22). If causally linked, these data suggest that prenatal tobacco exposure accounts for 270,000 excess cases of ADHD, and lead exposure accounts for 290,000 excess cases of ADHD in U.S. children. CONCLUSIONS: We conclude that exposure to prenatal tobacco and environmental lead are risk factors for ADHD in U.S. children.

PMID: 17185283 [PubMed - indexed for MEDLINE]

1: Neurotoxicology. 1998 Apr;19(2):283-91.Links
Lead potentiates cytokine- and glutamate-mediated increases in permeability of the blood-brain barrier.Dyatlov VA, Platoshin AV, Lawrence DA, Carpenter DO.
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509, USA.

We have measured the transendothelial electrical resistance across the blood-brain barrier (BBB) with a microelectrode technique and determined the effects of subcutaneous injections (five injections over ten days) of lipopolysaccharide (LPS, 100 ng/g), recombinant mouse interleukin-6 (IL-6, 5 ng/g), and/or inorganic lead (lead, 2.5 5 micrograms/g) on the ion permeability of arterioles in the temporoparietal cortex of anaesthetized mice between 10 and 40 days of age. In controls the electrical resistance increased with age. It was decreased in animals treated with IL-6, but unaffected by lead at the different ages studied. In IL-6 treated mice, repeated neonatal exposure to lead (five injections between 2 and 10 days after birth) caused a delay in the increase in arteriole resistance with age. LPS injections caused a 36% increase in ion permeability of the BBB in twenty-day-old mice, and lead potentiated this effect of LPS. Intra-arterial injections of glutamate did not alter vascular resistance, but topical applications of glutamate on the cerebrum caused a reversible decrease in the resistance in mice not treated with lead, and an irreversible decrease in mice treated with lead. Injections of glutamate in the lumen of arterial vessels in the parietal and temporoparietal brain areas of mice pretreated with lead and LPS, plus a topical application of glutamate, caused depolarization of neurons in the temporoparietal cortex. These results suggest that disruption of the BBB can allow serum glutamate to penetrate the brain, causing further disruption of the BBB, and that lead irreversibly potentiates this cascade of harmful events.

PMID: 9553965 [PubMed - indexed for MEDLINE]

1: Toxicol Lett. 2001 Sep 15;123(2-3):217-26. Links
Changes in mesocorticolimbic dopamine and D1/D2 receptor levels after low level lead exposure: a time course study.Gedeon Y, Ramesh GT, Wellman PJ, Jadhav AL.
Center for Toxicological Research, College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA.

Chronic post weaning low-level lead exposure produces cognitive deficits associated with Pb-induced alterations of mesocorticolimbic dopamine (DA) function. This study examined Pb-induced changes in the temporal profile of D1/D2 receptor protein and DA levels in the nucleus accumbens (NAC), hippocampus (HIP), and the frontal cortex (FC). Male Long-Evans rats were exposed to 0 (n=16-20) and 50 ppm Pb (n=16-20) for 180 days. Blood Pb analysis by atomic absorption spectroscopy showed BPb<2 microg/dl in the control group and BPb>9 microg/dl in the Pb-exposed group. Brain DA levels were evaluated by high performance liquid chromatography; D1/D2 receptor expressions, by autoradiographic analysis. Pb exposure produced a transient hyperdopaminergic state, followed by a sustained decline in dopaminergic function within the NAC and a longer-lasting hyperdopaminergic condition within the HIP, whereas it decreased FC D1/D2 without significantly affecting FC DA levels. These findings indicate that time plays a critical, region-specific role in Pb's effects on the normal synaptic profile of the mesocorticolimbic dopaminergic system.

PMID: 11641049 [PubMed - indexed for MEDLINE]

1: Arch Pediatr Adolesc Med. 2004 Dec;158(12):1113-5. Links
Comment in:
Arch Pediatr Adolesc Med. 2005 Aug;159(8):788; author reply 788.
Iron deficiency in children with attention-deficit/hyperactivity disorder.Konofal E, Lecendreux M, Arnulf I, Mouren MC.
Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, Paris, France. eric.konofal@rdb.ap-hop-paris.fr

BACKGROUND: Iron deficiency causes abnormal dopaminergic neurotransmission and may contribute to the physiopathology of attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To evaluate iron deficiency in children with ADHD vs iron deficiency in an age- and sex-matched control group. DESIGN: Controlled group comparison study. SETTING: Child and Adolescent Psychopathology Department in European Pediatric Hospital, Paris, France. PATIENTS: Fifty-three children with ADHD aged 4 to 14 years (mean +/- SD, 9.2 +/- 2.2 years) and 27 controls (mean +/- SD, 9.5 +/- 2.8 years). MAIN OUTCOME MEASURES: Serum ferritin levels evaluating iron stores and Conners' Parent Rating Scale scores measuring severity of ADHD symptoms have been obtained. RESULTS: The mean serum ferritin levels were lower in the children with ADHD (mean +/- SD, 23 +/- 13 ng/mL) than in the controls (mean +/- SD, 44 +/- 22 ng/mL; P < .001). Serum ferritin levels were abnormal (<30 ng/mL) in 84% of children with ADHD and 18% of controls (P < .001). In addition, low serum ferritin levels were correlated with more severe general ADHD symptoms measured with Conners' Parent Rating Scale (Pearson correlation coefficient, r = -0.34; P < .02) and greater cognitive deficits (r = -0.38; P < .01). CONCLUSIONS: These results suggest that low iron stores contribute to ADHD and that ADHD children may benefit from iron supplementation.

PMID: 15583094 [PubMed - indexed for MEDLINE]

1: Brain. 2003 Jan;126(Pt 1):5-19. Links
Lead neurotoxicity in children: basic mechanisms and clinical correlates.Lidsky TI, Schneider JS.
Center for Trace Element Studies and Environmental Neurotoxicology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. tlidsky@monmouth.com

Lead has been recognized as a poison for millennia and has been the focus of public health regulation in much of the developed world for the better part of the past century. The nature of regulation has evolved in response to increasing information provided by vigorous scientific investigation of lead's effects. In recognition of the particular sensitivity of the developing brain to lead's pernicious effects, much of this legislation has been addressed to the prevention of childhood lead poisoning. The present review discusses the current state of knowledge concerning the effects of lead on the cognitive development of children. Addressed are the reasons for the child's exquisite sensitivity, the behavioural effects of lead, how these effects are best measured, and the long-term outlook for the poisoned child. Of particular importance are the accumulating data suggesting that there are toxicological effects with behavioural concomitants at exceedingly low levels of exposure. In addition, there is also evidence that certain genetic and environmental factors can increase the detrimental effects of lead on neural development, thereby rendering certain children more vulnerable to lead neurotoxicity. The public health implications of these findings are discussed.

PMID: 12477693 [PubMed - indexed for MEDLINE]

1: Neuropsychol Rev. 2007 Mar;17(1):39-59. Links
Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis.Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, Taylor E, Casey BJ, Castellanos FX, Wadhwa PD.
Department of Pediatrics, University of California, Irvine, CA 92612, USA. jmswanso@uci.edu

Multiple theories of Attention-Deficit/Hyper-activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.

PMID: 17318414 [PubMed - indexed for MEDLINE]

1: Toxicol Appl Pharmacol. 2007 Feb 15;219(1):33-41. Epub 2006 Dec 8. Links
Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development.Wang Q, Luo W, Zheng W, Liu Y, Xu H, Zheng G, Dai Z, Zhang W, Chen Y, Chen J.
Department of Occupational and Environmental Health, Faculty of Military Preventive Medicine, Fourth Military Medical University, 17 Changlexi Street, Xi'an, 710032, China.

Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 microg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO(4) solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p<0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.

PMID: 17234227 [PubMed - indexed for MEDLINE]

1: Curr Opin Pediatr. 1999 Jun;11(3):255-8. Links
The role of iron therapy in childhood plumbism.Wright RO.
Rhode Island Hospital, Providence 02903, USA. rwright@rihosp.edu

Iron deficiency and lead poisoning share common environmental risk factors and both are causes of neurocognitive toxicity. Despite their links epidemiologically, little is known of the effects of iron supplements on lead kinetics and toxicity. Nevertheless, iron is routinely prescribed in children with lead poisoning. Most of the existing data focus on the effects of preexisting iron deficiency on lead absorption. Animal studies demonstrate that iron-deficient animals have increased lead absorption. Lead-poisoned iron-deficient animals treated with iron supplements have demonstrated decreased lead excretion, a factor that might exacerbate lead toxicity while mitigating the effects of iron deficiency. Iron supplements given to children with iron deficiency and lead poisoning have been demonstrated to improve developmental assessment scores, an effect that is independent of blood lead concentration, suggesting that it is solely due to reversal of iron deficiency. Improvements in developmental assessment scores and decreases in blood lead in iron-replete children with lead poisoning secondary to iron supplements have not been demonstrated in clinical studies. Given these factors, the use of iron supplements in lead poisoning should be individualized, and the supplements should be provided only to patients who are iron deficient or who continue to live in lead-exposed housing.

PMID: 10349106 [PubMed - indexed for MEDLINE]

[Jacovis]

The short article written below by Konofal and Cortese focus on the potential neuroprotective role of iron against the deleterious effect of lead on the development of ADHD symptoms...

http://www.pubmedcen...i?artid=1940080

Journal List > Environ Health Perspect > v.115(8); Aug 2007

PubMed articles by:
Konofal, E.
Cortese, S. Environ Health Perspect. 2007 August; 115(8): A398–A399.
doi: 10.1289/ehp.10304.
Copyright This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI
Perspectives
Correspondence
Lead and Neuroprotection by Iron in ADHD
Eric Konofal and Samuele Cortese
Child Psychopathology Unit, University Hospital Robert Debré, Paris, France, E-mail: eric.konofal@rdb.aphp.fr
The authors declare they have no competing financial interests.

We read with special interest the article by Braun et al. (2006). In this large survey, the authors concluded that prenatal exposure to tobacco and environmental lead are risk factors for attention deficit hyperactivity disorder (ADHD).
We would like to focus on the potential neuroprotective role of iron against the deleterious effect of lead on the development of ADHD symptoms.

Although the mechanisms underlying ADHD remain unclear, both genetic and environmental factors have been implicated. In a recent review on the implication of the dopaminergic system in the etiology of ADHD, Swanson et al. (2007) highlighted the importance of environmental risk factors as possible etiologies of dopamine deficit. Among these environmental factors, Swanson et al. (2007) cited the effects of lead exposure (at levels < 10 μg/dL) on ADHD-related behaviors and ADHD diagnosis.

Lead in the central nervous system may contribute to dopaminergic dysfunction inducing alteration of dopamine release and dopamine receptor density (Gedeon et al. 2001; Lidsky et al. 2003). Moreover, lead may disrupt the structure of the blood–brain barrier function essential for brain integrity (Dyatlov et al. 1998). Interestingly, Wang et al. (2007) recently reported that iron supplementation protects the integrity of the blood–brain barrier against lead insults. On the other hand, iron deficiency could increase the toxic effect of lead, suggesting a potent neuroprotective effect of iron supplementation on dopaminergic dysfunction due to lead exposure (Wright 1999; Wright et al. 2003)

In a controlled comparison group study, we (Konofal et al. 2004) showed that iron deficiency was correlated to ADHD symptoms severity, hypothesizing that iron supplementation may improve symptoms of ADHD in those subjects with low ferritin levels.

Given that lead exposure may contribute to ADHD and iron deficiency may exacerbate deleterious effects caused by lead, we recommend systematically seeking for iron deficiency in children with ADHD. We also think that controlled studies assessing the potential effectiveness of iron supplementation on ADHD symptoms should be encouraged. Such studies could aid the understanding of the complex pathophysiology underlying ADHD and provide effective therapeutic strategies for this disorder.

Below is some more correspondence regarding the article, "Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder [ADHD] in U.S. Children," by Braun et al. from Brondum and the reply from Braun et al. to the comments of both Brondum, and Konofal and Cortese...


Letter: Brondum J
Response: Braun JM, Lanphear BP, Kahn RS, Froehlich T, Auinger P

Environmental Exposures and ADHD

Environ Health Perspect 115:395-399 (2007). doi:10.1289/ehp.10274 available via http://dx.doi.org [Online 24 June 2007]

Referencing: Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder in U.S. Children

In their article, "Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder [ADHD] in U.S. Children," Braun et al. (2006) advanced our knowledge of the effects of environmental tobacco smoke (ETS) and lead on the central nervous system of children. With respect to lead exposure, the study, importantly, focused on an older age group (4–15 years) than is generally studied (< 6 years) because of the greater sensitivity of the developing central nervous system to environmental insult early in life [Centers for Disease Control and Prevention (CDC) 1997].

In the logistic model used by Braun et al. (2006), the association of ADHD with lead exposure was statistically significant in the highest exposure quintile; however, it was also tenuous. Although not unheard of, the cutoff (p < 0.2) for inclusion of factors and variables associated with ADHD on univariate analysis was generous compared with the commonly used 0.1 or 0.05, and very close to the p-value of the lead–ADHD association of 0.19. The lead–ADHD relationship also exhibited a significant monotonic dose response, so it would have been helpful to know how the authors developed their exposure metric. Why, for example, were quintiles selected rather than another interval scheme, and why were they not of uniform size? Was the reported dose response the only model considered, or did the authors investigate other models, as some have done in studying the relationship of lead exposure and cognition (Canfield et al. 2003)?

Braun et al. (2006) noted that their analyses were limited by the cross-sectional nature of the National Health and Nutrition Examination Survey data they used, precluding adjustment of their model for certain covariates and potential confounders (e.g., parental psychopathology). Based on data from multiple studies, ADHD heritability has been estimated to be about 75% (Biederman and Faraone 2005). Inability to adjust for parental psychopathology is therefore an important limitation, because adjustment would likely reduce—and might eliminate—the associations of ADHD with ETS and lead. In studies of lead exposure and cognition, some of which Braun et al. (2006) cited as being consistent with their findings, the strength of the IQ–lead relationship can be dwarfed by the relationship of IQ to other factors such as parenting and socioeconomic status (Koller et al. 2004). When reporting associations of environmental contaminants and pathology, it seems prudent to maintain a broader perspective, as well as an environmental health perspective.

The authors declare they have no competing financial interests.

Jack Brondum
Hennepin County Department of
Human Services and Public Health
Environmental Health and Epidemiology
Hopkins, Minnesota
E-mail: jack.brondum@co.hennepin.mn.us
References

Biederman J, Faraone SV. 2005. Attention-deficit hyperactivity disorder. Lancet 366: 237–248.

Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909.

Canfield RL, Henderson CR Jr, Cory-Schlechta DA, Cox C, Jusko TA, Lanphear BP. 2003. Intellectual impairment in children with blood lead concentrations below 10 µg per deciliter. N Engl J Med 348:1517–1526.

CDC. 1997. Screening Young Children for Lead Poisoning: Guidance for State and Local Public Health Officials. Atlanta, GA:Centers for Disease Control and Prevention.

Koller K, Brown T, Spurgeon, Levy L. 2004. Recent developments in low-level lead exposure and intellectual impairment in children. Environ Health Perspect 112: 987–994.


--------------------------------------------------------------------------------

ADHD: Braun et al. Respond

Environ Health Perspect 115:395-399 (2007). doi:10.1289/ehp.10274R available via http://dx.doi.org [Online 24 June 2007]

We appreciate the comments of Brondum, and Konofal and Cortese, and the opportunity to clarify our results (Braun et al. 2006). It is common practice to select variables with a p-value of 0.2 for inclusion in multivariable models (Katz 1999). Although the association of blood lead levels and ADHD appeared "tenuous" in bivariate analysis (i.e., p = 0.19), this was largely an artifact of our decision to categorize blood lead levels. When we entered lead into our multivariable analysis as a continuous variable, we found a 1.2-fold increased odds [95% confidence interval (CI), 1.0–1.4; p = 0.02] of ADHD for each 1.0-µg/dL increase in blood lead levels. The blood lead quintiles were not divided into exactly equal sample sizes because we used weighted percentages to categorize the data. We decided a priori to present the analysis in quintiles to make the results easier to interpret and also to illustrate any dose–response relationships for blood lead levels and ADHD.

As we noted in the "Discussion" of our article (Braun et al. 2006), a limitation of our study was the inability to adjust for parental psychopathology. This is an unfortunate trade-off when using a large nationally representative survey. In other studies, prenatal tobacco exposure has been shown to be a risk factor for the development of ADHD after controlling for parental psychopathology (Mick et al. 2002; Weissman et al. 1999). Although there is considerable experimental and epidemiologic evidence linking lead exposure with behaviors consistent with ADHD, future studies of childhood lead exposure will need to confirm our results by accounting for parental psychopathology and other potential confounders.

The hypothesis proposed by Konofal and Cortese—that iron deficiency may play a role in symptom severity among children with ADHD—is intriguing. Indeed, it was their original research that prompted us to incorporate ferritin as a measure of iron status (Konofal et al. 2004). It is certainly plausible that iron deficiency may confound or modify the effects of environmental lead exposure on ADHD in children. Alternatively, lead exposure may act as a confounder or modifier for the observed effects of iron deficiency with ADHD. Unfortunately, we were not able to examine whether ferritin (or other indicators of iron status) was associated with ADHD symptom severity using the National Health and Nutrition Examination Survey. Nor did we specifically test for an association between iron deficiency and ADHD. Although iron or other micronutrient supplementation may protect children from lead toxicity, recent evidence from a double-blind randomized trial (Kordas et al. 2005) suggests that iron and zinc supplementation did not appreciably lower blood lead levels or improve child behavior, as measured by the Conners Rating Scales. However, Kordas et al. included only children without anemia in their trial.

The authors declare they have no competing financial interests.

Joe M. Braun
Department of Epidemiology
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina
E-mail: jmbraun@unc.edu


Bruce P. Lanphear
Robert S. Kahn
Tanya Froehlich
Department of Pediatrics
Cincinnati Children's Hospital
Medical Center
Cincinnati, Ohio
E-mail: bruce.lanphear@chmcc.org


Peggy Auinger
Department of Pediatrics
University of Rochester School of Medicine
Rochester, New York
References

Braun JM, Froehlich TF, Kahn RS, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909.

Katz M. 1999. Multivariable Analysis: A Practical Guide for Clinicians. New York:Cambridge University Press.

Konofal E, Lecendreux M, Arnulf I, Mouren M. 2004. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 158:1113–1115.

Kordas K, Stoltzfus RJ, Lopez P, Rico JA, Rosado JL. 2005. Iron and zinc supplementation does not improve parent or teacher ratings of behavior in first grade Mexican children exposed to lead. J Pediatr 147:632–639.

Mick E, Biederman J, Faraone SV, Sayer J, Kleinman S. 2002. Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy. J Am Acad Child Adolesc Psychiatry 41:378–385.

Weissman MM, Warner V, Wickramaratne PJ, Kandel DB. 1999. Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood. J Am Acad Child Adolesc Psychiatry 38:892–899.

[mentatpsi]

hey before anyone adds one plus one, may i recommend a blood test due to the negative effects of iron. I don't think there's a simple solution to ADHD that involves just one supplementation (especially natural) and more importantly just a focal point on biological means. I know few were thinking to use it based on these research articles, but always good to make sure

[david ellis]

hey before anyone adds one plus one, may i recommend a blood test due to the negative effects of iron. I don't think there's a simple solution to ADHD that involves just one supplementation (especially natural) and more importantly just a focal point on biological means. I know few were thinking to use it based on these research articles, but always good to make sure

Yes, a blood test. And just not for serum iron, but for serum ferritin. Serum iron doesn't give much insight into how much iron is stored in the body. Serum Ferritin is the test that is needed. Ferritin is used to store iron in the the liver, heart, joints, gonads, pancrease, adrenals, thyroid gland, and skin. The empty ferritin "storage containers" that seep into the blood are an indication of how much iron is stored in the body. A ferritin level of 50 is a good target. 50 will more than cover the iron needed to replace a traumatic loss of blood. Excess iron storage is another symptom of metabolic syndrome. Three donations of blood might get you to target if you have a level under 300. LabCorp reference range is 22-322. People with both hemochromatosis gene can have a ferritin level of 3-4000. That is 30-40 grams of iron in the body. (Drs Eades-ProteinPowerLifefPlan)

[Jacovis]

Yes I agree with the others about making sure you get Ferritin levels tested before supplementing with something as potentially damaging as Iron. I think it is also very important (if you have ADHD-type symptoms) to test Lead levels given that this toxic metal is ment to be more damaging when Iron levels are low. I will post more about the damaging effects of Lead and its relationship to Iron in the future.


Below is another article which this time mentions a 20-week study with eight healthy men, aged 27 to 47 years. Kretsch looked at the relationship between iron and the volunteers' ability to concentrate. "We saw that a low score for volunteers' attention span corresponded with a subsequent decline in iron levels in the body." ... "In all studies," Kretsch reports, "cognitive changes were evident before biochemical changes occurred. This supports previous iron and zinc work with primates, which showed that cognitive changes can occur well ahead of other indicators of decreased iron or zinc. We think these cognitive tasks might prove to be a simple way to identify people who aren't getting enough iron or zinc—well before any signs show up in biochemical samples such as blood or urine."


http://www.ars.usda....1/brain1001.htm

Food for Thought: Studies Probe Role of Minerals in Brain Function

If you've been having trouble concentrating, maybe you're not getting enough of the nutrients your brain needs.
Studies by ARS physiologist Mary J. Kretsch and colleagues are revealing new clues about the roles essential nutrients apparently play in keeping our mental capacities—or what scientists call "cognitive function"—up to par. She is based at the ARS Western Human Nutrition Research Center in Davis, California.
Mental capabilities, such as memory and the ability to concentrate, are essential to carrying out responsibilities at home, work, and school. In the Information Age, especially, our mental productivity is critical to our success at work.

Yet, much of the research that links inadequate nutrition to mental performance has been done with children. And as Kretsch points out, "those studies have, for example, linked poor nutrition to impaired learning at school. Our work is with adults and focuses not on outright shortages of essential nutrients, but instead on marginal deficiencies."

Iron Decline Shortens Attention Span
In a 20-week study with eight healthy men, aged 27 to 47 years, Kretsch looked at the relationship between iron and the volunteers' ability to concentrate. "We saw that a low score for volunteers' attention span corresponded with a subsequent decline in iron levels in the body."
In an earlier study with 14 obese but otherwise healthy female volunteers, aged 25 to 42 years, Kretsch and colleagues had documented a similar change in ability to focus. The 21-week experiment showed that volunteers with borderline anemia, as measured by blood hemoglobin, were less able to concentrate than volunteers with higher hemoglobin. However, because blood hemoglobin can be influenced by nutrients other than iron, Kretsch measured other indicators of iron status, as well. Those tests also showed that iron status declined for those volunteers with the lower ability to concentrate.

Her studies are the first—in healthy adults—to link a decrease in iron with a decline in attention span. Kretsch says the findings suggest that decreased ability to concentrate may be an early indicator that an individual's iron levels are declining.
"Somewhat the same trend has been observed in studies elsewhere with children. It's been found, for instance, that children with iron deficiency anemia have a short attention span," Kretsch says."
We plan followup studies, with healthy adults, to investigate whether iron supplementation can reverse this cognitive impairment. We would also like to learn more about the mechanisms at work here."
Kretsch plans to recruit premenopausal women as volunteers for these next studies. That's because iron deficiency and iron-deficiency anemia are still relatively common in the United States among women of that age group, as well as among adolescent females.
Kretsch and co-workers measured volunteers' ability to concentrate by giving them a 6-minute-long standardized test. "We presented a continuous, fast-moving stream of single-digit numbers on a computer screen," she says. "We asked the volunteers to quickly press the space bar on the computer keyboard whenever they saw either three even or three odd numbers in a row. That may sound easy, but it's actually a demanding task that requires paying attention."

Low Zinc Leads to Faulty Memory
Kretsch and co-researchers also explored the interaction of brainpower and another nutrient, zinc. She worked with the same eight men who participated in the iron tests.
In one test of mental function, called verbal memory, the scientists evaluated the volunteers' ability to remember everyday words. "We showed the men a list of words on a computer screen. Then, we presented these words again, this time intermingled with new ones, and asked the volunteers to press a key whenever they recognized a word from the first list," says Kretsch.
Preliminary results showed that, after only 3 weeks on a low-zinc regimen, many of the volunteers' ability to recall the words slowed. The men who slowed the most in this test also had the greatest decrease in blood levels of zinc.
Several weeks later, while still in the low-zinc phase of the study, some of these volunteers more quickly identified what they thought were the correct words, but speed came at the expense of accuracy. "This trade-off of speed for accuracy," says Kretsch, "doesn't represent an improvement in their ability to adjust to a low-zinc regimen." The speed-for-accuracy response agreed with findings of a 1984 zinc study of healthy men, conducted by researchers at the ARS Grand Forks Human Nutrition Research Center.
"In all studies," Kretsch reports, "cognitive changes were evident before biochemical changes occurred. This supports previous iron and zinc work with primates, which showed that cognitive changes can occur well ahead of other indicators of decreased iron or zinc. We think these cognitive tasks might prove to be a simple way to identify people who aren't getting enough iron or zinc—well before any signs show up in biochemical samples such as blood or urine."

Kretsch's collaborators in the iron study included psychologist Michael W. Green of the Neurosciences Research Institute at Aston University, Birmingham, England, and—in the zinc study—psychologist James G. Penland of the ARS Grand Forks Human Nutrition Research Center. Among Kretsch's other co-investigators are Janet C. King, director of the ARS Western Human Nutrition Research Center; and Alice K.H. Fong, Herman L. Johnson, and Barbara Sutherland, formerly with the center.

The researchers have published their findings in the European Journal of Clinical Nutrition, the FASEB Journal, and in a book, Trace Elements in Man and Animals.—By Marcia Wood, Agricultural Research Service Information Staff.
This research is part of Human Nutrition, an ARS National Program (#107) described on the World Wide Web at http://www.nps.ars.usda.gov.
Mary J. Kretsch is with the USDA-ARS Western Human Nutrition Research Center, One Shields Ave., Davis, CA 95616; phone (530) 752-4171.

"Food for Thought: Studies Probe Role of Minerals in Brain Function" was published in the October 2001 issue of Agricultural Research magazine.

[Jacovis]

On the other hand, the study below seems to show that lower ferritin levels were associated with higher hyperactivity scores in parental ratings in the study's sample but not significantly related with cognitive performance...

1: Pediatr Int. 2008 Feb;50(1):40-4. Links
Relation of ferritin levels with symptom ratings and cognitive performance in children with attention deficit-hyperactivity disorder.Oner O, Alkar OY, Oner P.
Department of Child Psychiatry, SB Diskapi Children's Hospital, Ankara, Turkey. ozz_oner@yahoo.com

BACKGROUND: The aim of the present paper was to investigate the relationship between behavioral symptoms and attentional and executive functions and hematological variables related to iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and red cell distribution width (RDW) in children and adolescents with attention deficit-hyperactivity disorder (ADHD). METHODS: The sample consisted of 52 ADHD children (42 boys, 10 girls; age 7-13 years; mean +/- SD, 9.9 +/- 2.1 years). Conners Parent and Teacher Rating Scales were obtained. The neuropsychological test battery included Wisconsin Card-Sorting Test (WCST), Stroop, Continuous Performance Test, Digit Symbol and Digit Span subtests of the Wechsler Intelligence Scale for Children Revised (WISC-R), and Trail Making Test A and B, which taps abstraction-flexilibity (WCST), sustained attention (CPT), mental tracking and complex attention (WISC-R Digit Span, Digit Symbol, Trail Making A and B) and interference control (Stroop). Multiple linear regression was used to evaluate the relation of ferritin, hemoglobin, MCV, RDW, age, gender, and presence of comorbidity. RESULTS: While seven children had iron deficiency, none of them was anemic. Lower ferritin levels were associated with higher hyperactivity scores in parental ratings. While performance increased with age for most of the neuropsychological tests utilized, ferritin, hemoglobin, MCV and RDW and gender were not significantly related with cognitive performance in this sample. CONCLUSIONS: At least for the present clinical sample, ferritin levels might be related with behavioral but not cognitive measures in ADHD cases.

PMID: 18279203 [PubMed - indexed for MEDLINE]

[Jacovis]

1: Eur Child Adolesc Psychiatry. 2009 Feb 5. [Epub ahead of print] Links
Sleep disturbances and serum ferritin levels in children with attention-deficit/hyperactivity disorder.

Cortese S, Konofal E, Bernardina BD, Mouren MC, Lecendreux M.
AP-HP, Child and Adolescent Psychopathology Unit, Robert Debré Hospital, Paris VII University, Paris, France, samuele.cortese@gmail.com.
BACKGROUND: A subset of children with attention-deficit/hyperactivity disorder (ADHD) may present with impairing sleep disturbances. While preliminary evidence suggests that iron deficiency might be involved into the pathophysiology of daytime ADHD symptoms, no research has been conducted to explore the relationship between iron deficiency and sleep disturbances in patients with ADHD. The aim of this study was to assess the association between serum ferritin levels and parent reports of sleep disturbances in a sample of children with ADHD. METHODS: Subjects: Sixty-eight consecutively referred children (6-14 years) with ADHD diagnosed according to DSM-IV criteria using the semi-structured interview Kiddie-SADS-PL. Measures: parents filled out the Sleep Disturbance Scale for Children (SDSC) and the Conners Parent Rating Scale (CPRS). Serum ferritin levels were determined using the Tinaquant method. RESULTS: Compared to children with serum ferritin levels >/=45 microg/l, those with serum ferritin levels <45 microg/l had significantly higher scores on the SDSC subscale "Sleep wake transition disorders" (SWTD) (P = 0.042), which includes items on abnormal movements in sleep, as well as significantly higher scores on the CPRS-ADHD index (P = 0.034). The mean scores on the other SDSC subscales did not significantly differ between children with serum ferritin >/=45 and <45 microg/l. Serum ferritin levels were inversely correlated to SWTD scores (P = 0.043). CONCLUSION: Serum ferritin levels <45 microg/l might indicate a risk for sleep wake transition disorders, including abnormal sleep movements, in children with ADHD. Our results based on questionnaires set the basis for further actigraphic and polysomnographic studies on nighttime activity and iron deficiency in ADHD. Research in this field may suggest future trials of iron supplementation (possibly in association with ADHD medications) for abnormal sleep motor activity in children with ADHD.
PMID: 19205783 [PubMed - as supplied by publisher]

[bgwithadd]

My guess is that ADHD doesn't have any one cause. It is probably due to about a hundred causes, which is probably why people respond well to much different treatments (some even seem to respond to alcohol and even pot). If some have it due to iron deficiency my guess is they have some flaw that does not allow them to properly retain iron, not that their diet is deficient. Sort of like how it now seems autism is due to being unable to properly utilize b12. I know that my iron levels are high due to giving blood, anyway.

My guesses for some big causes are:

1. Brain damage - probably more often the case than many might expect, and can have any number of causes or even be due to simple unlucky rowth pattern for the brain/bad brain structure. ADD is seen as a bunk disease by many due to being 'overdiagnosed' in the US (even though evidence shows most cases go undiagnosed), but the US also has the shittiest diet on the planet, including a plethora of food additives that are known to cause neurotoxicity and an absolutely insane amount of sugar. In people with a weakened BBB (which is almost completely a mystery) or who don't have proper levels of growth factors etc. to make new cells or simply have fewer receptors to start with, this could cause massive problems. Sugar is obviously one of the least healthy things out there, and could lead to brain problems through exicotoxicity, insulin reaction, or I'm sure any number of ways.
2. Neurodegeneration - similar to the first one, I guess, but more specific causes. Due to genetic problems that cause too much cell death, weak neuronal sheathes, overexcitable neurons, etc.
3. Overactive MAO-B. Not enough phenylethylamine and dopamine transport in the brain.
4. cAMP levels messed up due to chronic anxiety or other reasons. Closes down prefrontal cortex.
5. Inability to properly produce or absorb substances like ATP and SAMe or selenium or zinc. Could have many mechanisms.

[StrangeAeons]

For the record I started seeing an orthomolecular psychiatrist recently (see my thread on Orthomolecular Regimens) and he sent out for a boatload of labs. My symptoms are partially, but not entirely ADD, as they seem to traverse a whole host of neurotic diagnoses. I do have trouble with planning, focusing on things I do not care about, paying attention, etc.
My iron came back severely deficinet, serum iron was 23, ferritin was 5, TIBC elevated and saturation was 5%; and yes, bgwithadd, my doctor and I both came to the conclusion that this was an absorption issue and not a dietary deficiency. That's why a very crucial part of my regimen is heavy probiotic and glutamine supplementation. Once I've had a couple of months of both these GI supps and heavy iron supplementation, I'll let you know if symptoms improve. A little case study, if you will.
Granted, there are probably a slew of other explanations for ADD/ADHD. I think it's fair to say that like many other psychiatric diagnoses, it should be regarded only as a differential in the absence of a concrete pathophysiology. To dismiss these things as idiosyncratic is bad medicine, and we should seek out an empirical root cause instead of merely patching up symptoms.
I am, however, a little skeptical of out and out brain damage. A leaky blood brain barrier is probably going to indicate more prominent neuropsychiatric features than poor focus. I'm all too wary of this sweeping invection, "we're all eating toxins!" It may be a terrible diet, but it takes quite a bit to directly assault the brain. An insulin reaction seems like a pretty poor fit, too. You're essentially insinuating that the brain damage would occur through postprandial hypoglycemia. If such a reaction were to occur at a level that was damaging to the brain, it would present rather acutely with decreased level of consciousness. This kind of thing is unlikely to happen in anybody but diabetics and hyperthyroid patients.

[bgwithadd]

Well, it's just speculation, but brain damage doesn't have to be obvious. Some things in the brain are much more delicate than others - such as dopamine receptors. Simply going into the brain and causing extra excitatory action is enough to cause brain damage, especially damage to the areas that ADD meds bind to. If you have something in the brain wrong like a more permeable BBB or else not enough inhibitory neurotransmitters, it could cause much more damage compared to someone else. Much how phenalalanine really causes problems for some people who can't metabolise it as rapidly. Its metabolites are neurotoxic to everyone, but it has a much more dramatic effect in people with that disorder. I'd not be surpised to learnt here are a dozen similar disorders that have not been detected because they are milder in their effects.

I also think that some of it may not be so much damage as just random growth patterns - if not enough blood vessels grow to the right places in the brain, you are out of luck. I think that possibly explains why some twins get ADHD or schizophrenia and some don't. I really don't believe it's due to 'thought patterns' or watching tv or anything ridiculous like that - if you look at PET scans there are areas of the brain that just don't get enough blood and are not active enough for people with ADD or many other mental disorders. Bad nutrition could come into play here, though, as well. People like to blame bad parenting for everything, but I had fine parents and many/most people with terrible parents turn out absolutely fine.

[stephen_b]

I have a different hypothesis: people low in iron might be so because harmful gut bacteria are scavenging it all, creating neurotoxins, and contributing to ADHD symptoms. Iron supplementation in that case could be harmful.

StephenB

[StrangeAeons]

I have a different hypothesis: people low in iron might be so because harmful gut bacteria are scavenging it all, creating neurotoxins, and contributing to ADHD symptoms. Iron supplementation in that case could be harmful.

StephenB

The body reacts to infection by scavenging iron; anemia due to infection results in decreased serum iron, but increased ferritin. If you take a C-Reactive protein with the iron labs you can gauge whether this is a deficiency or a reaction to infection; further rule out for infection can be done with cultures and endoscopy. Deficiency seems like a better fit. These studies cite low ferritin levels as correlates of behavioral problems. Iron is actual an essential cofactor for catecholamine synthesis.