Schindeler 2007.

Methods	Randomised controlled cross‐over trial.
Participants	Number of participants: 16 enrolled, ages 11 to 45 years. Inclusion criteria: diagnosed with classical PKU; early initiation of treatment; currently treated by a protein‐restricted diet supplemented with protein substitute. Exclusion criteria: none indicated.
Interventions	4‐arm trial; each arm lasted 14 days separated with washout periods of at least 4 weeks. Participants were instructed to remain on a low‐phenylalanine diet through the entirety of the trial. 1. Placebo without protein substitute 2. Placebo plus protein substitute Not included in this review: 3. LNAAs plus protein substitute 4. LNAAs without protein substitute
Outcomes	1. Neuropsychological performance (attention, reaction time, response inhibition, generativity, self‐monitoring, cognitive flexibility, planning, immediate span, and working memory) 2. Plasma phenylalanine concentrations 3. Plasma phenylalanine: tyrosine ratio 4. Intakes of total protein, protein from protein substitute, protein from food, and phenylalanine 5. Brain phenylalanine concentrations Not included in this review: 6. Self‐reported ratings of mood 7. LNAA intake
Notes	Location: Australia
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Generation of allocation sequence: randomization process not described.
Allocation concealment (selection bias)	Low risk	Adequate.
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants, investigators, and outcome assessor were blinded to treatment allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomized participants are included in the final analysis of neuropsychological performance, plasma phenylalanine and tyrosine concentrations, and brain phenylalanine concentrations. Two participants were excluded from diet analyses due to failure to submit diet records in at least one of the trial arms.

LNAA: large neutral amino acid
 PKU: phenylketonuria
 RCT: randomised controlled trial
 RDA: recommended daily allowance