Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial

Randomized controlled trial in infants with Down’s syndrome recruited from Greater London, the West Midlands, Nottingham, and south west England between May 2002 and February 2004. The active intervention arms included antioxidants plus folinic acid (N=41), antioxidants only (N=40), and folinic acid only (N=36); participants were under 7 months of age at enrollment.

Infants were randomized to daily oral antioxidant supplements, folinic acid, or the combination. The antioxidant regimen contained selenium 10 μg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg; folinic acid was 0.1 mg. Doses were increased by 30% after the child’s first birthday and continued until the 18-month assessment; placebo contained mannitol, maltodextrin, and natural food colour.

Daily antioxidant and/or folinic acid supplementation did not improve psychomotor development or language in young children with Down’s syndrome. In the antioxidants comparison, Griffiths Total GQ was 58.1 (9.5) versus 56.9 (10.8), difference 1.2 (-2.2 to 4.6), and hearing and language was 56.5 (10.3) versus 56.8 (14.3), difference -0.3 (-4.5 to 3.9). Biochemical markers were also essentially unchanged, including SOD-1 4.0 (1.1) versus 3.8 (1.1), GSH-Px 66.3 (34.8) versus 65.3 (37.7), and urinary isoprostanes 2264 (2202) versus 2306 (2399), ratio 1.10 (0.61 to 2.00). Antioxidant treatment increased plasma vitamin E (10.76 vs 5.92; P<0.0001) but also caused more vomiting or distress leading to stopping supplements, 10/74 versus 0/65 (P=0.002).

The active arms were modest in size, which limits power to detect small or subgroup-specific effects. Follow-up was limited to early childhood with outcomes assessed to 18 months, so longer-term developmental effects cannot be excluded. Several biochemical and developmental endpoints were assessed, increasing the chance of chance findings while still showing no clinically meaningful benefit.