Related Experiment Video
Updated: Jul 11, 2026
Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
Protein substitute dosage in PKU: how much do young patients need?
A MacDonald1, A Chakrapani, C Hendriksz
1Birmingham Children's Hospital, Birmingham, UK. anita.macdonald@bch.nhs.uk
Insights
A lower protein substitute dose in phenylketonuria (PKU) increased blood phenylalanine levels. Higher protein substitute doses appear necessary for optimal phenylalanine control in children with PKU.
Area of Science:
- Biochemistry
- Pediatric Nutrition
- Metabolic Disorders
Background:
- Optimal protein substitute dosage remains undetermined for children with phenylketonuria (PKU).
- Current UK Medical Research Council (MRC) recommendations guide protein substitute dosing.
Purpose of the Study:
- To compare the efficacy of a lower protein substitute dose against the standard UK MRC-recommended dose in managing blood phenylalanine levels in children with PKU.
Main Methods:
- A six-week randomized crossover study involving 25 children (aged 2-10 years) with well-controlled PKU.
- Two protein substitute doses were administered: 2 g/kg/day (Protocol A) and 1.2 g/kg/day (Protocol B) for 14 days each, with a 14-day washout period.
- Plasma phenylalanine levels were monitored twice daily during the final week of each protocol.
Main Results:
- The lower protein substitute dose (1.2 g/kg/day) resulted in a significant increase in median plasma phenylalanine levels (301-337 mumol/l).
- The higher protein substitute dose (2 g/kg/day) maintained phenylalanine levels comparable to baseline/control values.
- Significant inter-individual variability in response to protein substitute dosage was observed.
Conclusions:
- Higher protein substitute dosages appear more effective in reducing blood phenylalanine concentrations in children with PKU.
- The impact of protein substitute dosage on phenylalanine control is variable and individualized.
- Carbohydrate and fat content of the protein substitute may influence its efficacy.
Background:
The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU).
Aim:
To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1)
Methods:
In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day).
Results:
When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects.
Conclusions:
A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.
Related Concept Videos
01:20Inborn Errors of Metabolism
01:29Drug Dosing: Infants and Children
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:28Chronic Kidney Disease III: Interprofessional Care