Abstract: Children with phenylketonuria (PKU) follow a protein restricted diet with negligible
amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits
in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual
functioning in PKU. In a double-blind multicentric trial, 109 PKU patients were randomized to DHA
doses from 0 to 7 mg/kg&day for six months. Before and after supplementation, we determined
plasma fatty acid concentrations, latencies of visually evoked potentials, fine and gross motor
behavior, and IQ. Fatty acid desaturase genotypes were also determined. DHA supplementation
increased plasma glycerophospholipid DHA proportional to dose by 0.4% DHA per 1 mg intake/kg
bodyweight. Functional outcomes were not associated with DHA status before and after intervention
and remained unchanged by supplementation. Genotypes were associated with plasma arachidonic
acid levels and, if considered together with the levels of the precursor alpha-linolenic acid, also with
DHA. Functional outcomes and supplementation effects were not significantly associated with
genotype. DHA intakes up to 7 mg/kg did not improve neurological functions in PKU children.
Nervous tissues may be less prone to low DHA levels after infancy, or higher doses might be required
to impact neurological functions. In situations of minimal dietary DHA, endogenous synthesis of
DHA from alpha-linolenic acid could relevantly contribute to DHA status.