Doses up to 30 mg/day of zinc were safe for at least 8 weeks, but clinical effect was equivocal except for 37% reduction in amphetamine optimal dose with 30 mg/day zinc (not with 15 mg). Possible reasons for difference from mideastern reports include endemic diets, population genetics, relative rate of zinc deficiency, difference in background nutrition, insufficient dosage or absorption, or wrong anion (sulfate may be necessary for reported benefit). Dose may be especially important: All visually impressive advantages over placebo appeared only with 15 mg b.i.d. rather than once a day. Future research should use larger doses than 15 mg/day, provide a basic recommended daily allowance/intake multivitamin/mineral supplement for all to standardize background nutrition, select participants for low zinc, and consider the issue of anion interaction.

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.

ALC appears safe, but with no effect on the overall ADHD population (especially combined type). It deserves further exploration for possible benefit specifically in the inattentive type.

This study illustrates the importance of a credible control condition of equal duration and intensity in trials of novel treatments. CMA treatment cannot be recommended for combined-type ADHD without learning disorder.