Research Notes: Zinc

U.S. RDAs

Infants 0-6 months: 2 mg, not to exceed 4 mg
Infants 7 months-1: 3 mg, not to exceed 5 mg
Toddlers 1-3: 3 mg, not to exceed 10 mg
Children 4-8: 5 mg, not to exceed 12 mg
Children 9-13: 8 mg, not to exceed 23 mg

Adolescents 14-18

• Males: 11 mg, not to exceed 34 mg
• Females: 9 mg, not to exceed 34 mg
  • Pregnant: 13 mg, not to exceed 34 mg
  • Lactating: 14 mg, not to exceed 34 mg

Adults 18+

• Males: 11 mg, not to exceed 40 mg
• Females: 8 mg, not to exceed 40 mg
  • Pregnant: 11 mg, not to exceed 40 mg
  • Lactating: 12 mg, not to exceed 40 mg

Sources

J Child Adolesc Psychopharmacol. 2005 Aug.
Zinc in attention-deficit/hyperactivity disorder.
Arnold LE, DiSilvestro RA.
Department of Psychiatry, Ohio State University, Columbus, OH, USA.

Objective: The aim of this study was to review the published evidence for a role of zinc nutrition in attention-deficit/hyperactivity disorder (ADHD). Method: A computer literature search was supplemented by the authors' knowledge. Results: Numerous controlled studies report cross-sectional evidence of lower zinc tissue levels (serum, red cells, hair, urine, nails) in children who have ADHD, compared to normal controls and population norms. A few studies show correlations of zinc level with either clinical severity or a change thereof in response to stimulant or chemical challenge. Two placebo-controlled trials - one of zinc monotherapy, the other of zinc supplementation of methylphenidate - reported significant benefit. However, diagnostic procedures and sample representativeness were often not clear, and most such reports have come from countries and cultures with different diets and/or socioeconomic realities than are found in the United States (only one American sample in nine published reports). In particular, both positive clinical trials of zinc supplementation came from the Mid-East (Turkey and Iran), an area with suspected endemic zinc deficiency. The largest of these trials used zinc doses above the recommended upper tolerable limit and had a 2 in 3 dropout rate. Conclusion: It is not clear how well the accumulating evidence for a possible role of zinc in ADHD applies to middle-class American children. However, the evidence appears strong enough to warrant further controlled study in well-diagnosed samples representative of the socioeconomic spectrum. Hypothesis-testing clinical trials are needed of this potential treatment that, if found effective, might become a relatively safe, cheap substitute for, or adjunct to, current treatments in some patients. At present, it should remain an investigational treatment.

J Child Adolesc Psychopharmacol. 2005 Aug.
Serum zinc correlates with parent- and teacher-rated inattention in children with attention-deficit/hyperactivity disorder.
Arnold LE, Bozzolo H, Hollway J, Cook A, DiSilvestro RA, Bozzolo DR, Crowl L, Ramadan Y, Williams C.
Department of Psychiatry, Ohio State University, Columbus, Ohio, USA.

Objective: The aim of this study was to explore the relationship of zinc nutrition to the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms in a middle-class American sample with well-diagnosed ADHD. Previous reports of zinc in ADHD, including two positive clinical trials of supplementation, have come mainly from countries and cultures with different diets and/or socioeconomic realities. Method: Children 5-10 years of age with DISC- and clinician-diagnosed ADHD had serum zinc determinations and parent and teacher ratings of ADHD symptoms. Zinc levels were correlated (Pearson's and multiple regression) with ADHD symptom ratings. Results: Forty-eight children (37 boys, 11 girls; 33 combined type, 15 inattentive) had serum zinc levels with a median/mode at the lowest 30% of the laboratory reference range; 44 children also had parent/teacher ratings. Serum magnesium levels were normal. Nutritional intake by a parent-answered food frequency questionnaire was unremarkable. Serum zinc correlated at r = -0.45 (p = 0.004) with parent-teacher-rated inattention, even after controlling for gender, age, income, and diagnostic subtype, but only at r = -0.20 (p = 0.22) with CPT omission errors. In contrast, correlation with parent-teacher-rated hyperactivity-impulsivity was nonsignificant in the opposite direction. Conclusion: These findings add to accumulating evidence for a possible role of zinc in ADHD, even for middle-class Americans, and, for the first time, suggest a special relationship to inattentive symptoms. They do not establish either that zinc deficiency causes ADHD nor that ADHD should be treated with zinc. Hypothesis-testing clinical trials are needed.

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan.
Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder.
Bilici M, Yildirim F, Kandil S, Bekaroglu M, Yildirmis S, Deger O, Ulgen M, Yildiran A, Aksu H.
Department of Psychiatry, Medical Faculty, Karadeniz Technical University, School of Medicine, Trabzon, Turkey.

Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. Methods: Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.

J Child Adolesc Psychopharmacol. 2000 Summer.
Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?
Arnold LE, Pinkham SM, Votolato N.
Department of Psychiatry, Ohio State University, Columbus, USA.

Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition.

J Child Psychol Psychiatry. 1996 Feb.
Relationships between serum free fatty acids and zinc, and attention deficit hyperactivity disorder: a research note.
Bekaroglu M, Aslan Y, Gedik Y, Deger O, Mocan H, Erduran E, Karahan C.
Department of Psychiatry, Technical University, Faculty of Medicine, Trabzon, Turkey.

The purpose of this study is to evaluate the relationships between serum free fatty acids (FFA) and zinc, and attention deficit hyperactivity disorder (ADHD). Forty eight children with ADHD (33 boys, 15 girls) were included in the patient group and 45 healthy volunteer children (30 boys, 15 girls) constituted the control group. The mean serum FFA level in the patient group was 0.176 +/- 0.102 mEq/L and in control group, 0.562 +/- 0.225 mEq/L (p < .001). The mean serum zinc level of patient group was 60.6 +/- 9.9 micrograms/dl and that of the control group, 105.8 +/- 13.2 micrograms/dl (p < .001). A statistically significant correlation was found between zinc and FFA levels in the ADHD group. These findings indicate that zinc deficiency may play a role in aetiopathogenesis of ADHD. Although we observed decreased FFA levels in ADHD cases, it is necessary to determine whether this condition is a principal cause of ADHD or is secondary to zinc deficiency.