SynthesisNutrients2021
Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis.
Synthesis in Nutrients, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 5 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 5 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Meta-analysis of bone mineral density in adults with phenylketonuria.Orphanet journal of rare diseases · 2024Pooled it
- Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Nutrition management of PKU with pegvaliase therapy: update of the web-based PKU nutrition management guideline recommendations.Orphanet journal of rare diseases · 2023Guideline
- Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?Nutrients · 2022Pooled it
- Pooled it
- Article
- Observational
- Navigating adulthood with PKU: metabolic outcomes, quality of life, and mental health 4.5 years post-transition.Orphanet journal of rare diseases · 2026Article
- Personalized, digitally designed 3D-Printed protein substitutes: Advancing medical food for PKU patients.Current research in food science · 2026Article
- Improving sapropterin administration efficacy in PKU: Clinical practice case studies.Molecular genetics and metabolism reports · 2025Article
- Risk of inadequate protein and micronutrient intakes in patients with PKU with an increased phe-tolerance: Impact of a micronutrient-dense protein substitute.Molecular genetics and metabolism reports · 2025Article
- Nutritional management of metabolic disorders in neonates and infants in Saudi Arabia: consensus recommendations.Orphanet journal of rare diseases · 2025Article
- Patient journey and disease burden characterization of the population with phenylketonuria (PKU) in Brazil: a retrospective analysis through data reported in the public health system administrative database (DATASUS).Lancet regional health. Americas · 2025Article
- A Cross-Sectional Study on Protein Substitutes for Paediatric Phenylketonuria Diet: Time to Pay Attention.Nutrients · 2025Article
- Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity.Nutrients · 2024Article
- Maximal dietary responsiveness after tetrahydrobiopterin (BH4) in 19 phenylalanine hydroxylase deficiency patients: What super-responders can expect.Molecular genetics and metabolism reports · 2024Article
- Total Protein Intake in Patients with PKU: Adequacy Evaluation According to the European PKU Guidelines from 2017.Nutrients · 2023Article
- Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria.Nutrients · 2023Article
- Impact on Diet Quality and Burden of Care in Sapropterin Dihydrochloride Use in Children with Phenylketonuria: A 6 Month Follow-Up Report.Nutrients · 2023Observational
- Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.Molecular genetics & genomic medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The traditional treatment for phenylketonuria (PKU) is a phenylalanine (Phe)-restricted diet, supplemented with a Phe-free/low-Phe protein substitute. Pharmaceutical treatment with synthetic tetrahydrobiopterin (BH4), an enzyme cofactor, allows a patient subgroup to relax their diet. However, dietary protocols guiding the adjustments of protein equivalent intake from protein substitute with BH4 treatment are lacking. We systematically reviewed protein substitute usage with long-term BH4 therapy. Electronic databases were searched for articles published between January 2000 and March 2020. Eighteen studies (306 PKU patients) were eligible. Meta-analyses demonstrated a significant increase in Phe and natural protein intakes and a significant decrease in protein equivalent intake from protein substitute with cofactor therapy. Protein substitute could be discontinued in 51% of responsive patients, but was still required in 49%, despite improvement in Phe tolerance. Normal growth was maintained, but micronutrient deficiency was observed with BH4 treatment. A systematic protocol to increase natural protein intake while reducing protein substitute dose should be followed to ensure protein and micronutrient requirements are met and sustained. We propose recommendations to guide healthcare professionals when adjusting dietary prescriptions of PKU patients on BH4. Studies investigating new therapeutic options in PKU should systematically collect data on protein substitute and natural protein intakes, as well as other nutritional factors.
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