Where food meets medicine Improving treatment access in inherited metabolic diseases

Inherited metabolic diseases (IMDs) are a heterogeneous group of genetic disorders that can impair the body's ability to process specific nutrients. For many IMDs, management relies on nutritional therapy products (NTPs), such as single amino acids, vitamins, and cofactors, which can function as medicines, yet are often only available as foods or food supplements.
This thesis examines the regulatory and clinical consequences. In Part I, the EU regulatory framework for NTPs in IMD management is analyzed. The distinction between food and medicine has significant implications for quality, safety monitoring, and patient access and a flowchart is proposed to aid differentiation. A survey among European metabolic healthcare professionals showed that authorized treatment products for urea cycle disorders are more consistently available, though their higher costs create new access barriers. Case reports illustrate the risks of food-grade NTPs, including life-threatening treatment gaps in PNPO deficiency and less structured safety monitoring.
Part II identifies essential NTPs that functionally operate as medicines. An international Delphi process established a reference list of essential NTPs, with systematic reviews confirming the clinical benefit of riboflavin (vitamin B2) in four IMDs and pyridoxal-5′-phosphate (vitamin B6 vitamer) in PNPO deficiency.
Part III proposes pathways to improve patient access, including a regulatory roadmap for academics and a framework for socially responsible public–private partnerships to support sustainable medicine development.
Overall, this thesis shows that NTPs in IMD management occupy a regulatory grey zone, calling for stronger evidence generation and improved regulatory pathways to ensure safe and appropriate treatment access.