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Large-scale trials are only available for BH 4 , sepiapterin or sapropterin in phenylketonuria (Muntau et al., 2024), an autosomal recessive disorder caused by deficiency of phenylalanine hydroxylase, leading to hyperphenylalaninemia, developmental delay, behavioral problems, and reduced quality of life ( Approaches with preclinical evidence only Promoting transcriptional regulation of eNOS Several compounds have been identified to enhance eNOS transcription and promote NO production