Sapropterin

Effective in a subset of PKU patients with BH4-responsive mutations. Interest in broader neurotransmitter support is based on BH4's cofactor role but not yet clinically validated outside PKU.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Phase III trials demonstrated significant reduction in blood phenylalanine in BH4-responsive PKU patients. BH4 is also a cofactor for NOS (nitric oxide synthase), TH (tyrosine hydroxylase), and TPH (tryptophan hydroxylase), leading to interest in mood and vascular applications. Non-PKU applications lack robust trial data.

• FDA-approved for BH4-responsive PKU
• Essential cofactor for monoamine neurotransmitter synthesis
• Reduces blood phenylalanine and allows dietary flexibility in PKU

PKU: 10–20 mg/kg/day once daily with food. Dose titrated based on phenylalanine response.

• Headache
• Rhinorrhea
• Diarrhea
• Pharyngolaryngeal pain

Prescription-only. Must verify BH4 responsiveness before initiating in PKU. GI side effects and headache are common. Monitor amino acid levels.

PKU application is well-validated. Broader nootropic or mood applications are theoretical and not supported by clinical trials.

• Mood25
• Focus20