Essential Oral Single Nutritional Therapy Products for Inherited Metabolic Diseases: Evidence and Consensus Assessment Using a Modified Delphi Method

Abstract

Nutritional therapy is critical in managing inherited metabolic diseases (IMDs), and includes specialized diets and single nutritional therapy products (sNTPs) such as vitamins, cofactors, and amino acids. Many sNTPs function as medicines, but are regulated as food (e.g., food supplements), which can limit access, reimbursement, and consistent supply. Essential medicines, as defined by World Health Organization (WHO), meet key healthcare needs and must be available, affordable, and quality-assured. Some sNTPs might meet this threshold, supporting their potential inclusion in the WHO essential medicines list. A modified Delphi process was conducted with a panel of 36 experts from 18 European countries to identify which sNTPs are essential for IMD treatment. Ninety-six sNTPs and their target IMDs were assessed using a literature-informed five-criteria framework, that included evaluation of the level of scientific evidence for usefulness and effectiveness. Overall, 31 sNTPs were deemed essential in the management of 55 IMDs, consisting of vitamins (n = 12), minerals (n = 4), amino acids (n = 6), sugars (n = 2), and other nutrients (n = 7). Evidence supporting their use ranged from levels 3 to 4 of the Oxford Centre for Evidence-Based Medicine (OCEBM), reflecting the limited clinical trial data inherent to rare diseases. Seven of these are already included in the WHO essential medicines list. Recognition of the remaining 24 essential sNTPs could improve their availability and reimbursement, and in some cases, may warrant formal authorization as medicines. Subsequent research should focus on access inequities, cost barriers, and incorporate patient perspectives to optimize the use and impact of sNTPs in IMD management.