Level 2: Mid-level evidence

Artificial colors and/or sodium benzoate might increase hyperactivity in children, based on a randomized crossover trial of 153 children aged 3-4 years and 144 children aged 8-9 years in Southampton, U.K. (Lancet. 2007;370:1560-1567). After one week of typical diet (baseline) and one week of withdrawal diet plus placebo drink, children were given drink A (mixed fruit juices containing 20 or 24.98 mg artificial food coloring and 45 mg sodium benzoate), drink B (mixed fruit juices containing 30 or 62.4 mg artificial food coloring and 45 mg sodium benzoate), or placebo for one week each with one-week washout period between treatments. Higher doses of artificial food coloring were used for older children. At study’s end, 137 (89.5%) children aged 3-4 years and 130 (90%) children aged 8-9 years remained.

The primary outcome was global hyperactivity aggregate (GHA)—a composite of abbreviated teacher rating, parent rating, direct classroom observation, and (for children aged 8-9 years) computerized continuous performance test. The estimated marginal means for GHA were lower with placebo than with either study drink. In children aged 3-4 years, the difference with drink A reached statistical significance only in a subgroup of children with ≥85% consumption; the difference with drink B did not reach statistical significance. In children aged 8-9 years, the difference with drink A reached statistical significance only in a subgroup of children with 100% consumption; the difference with drink B was statistically significant, but the difference may not be clinically relevant.