LEVELS: Per CODEX CXS 72-1981, optional ingredients should 'provide substances ordinarily found in human milk and ensure that the formulation is suitable as the sole source of nutrition for the infant or to provide other benefits that are similar to outcomes of populations of breastfed babies.' If safety is established, should a minimum effective level be established for optional ingredients?
Results
(14 Answers)
Experts are divided on whether minimum effective levels should be required for optional ingredients in infant formula, with responses falling into three main camps:
Support for Minimum Effective Levels (4 experts): These experts argue that minimum levels are essential to ensure meaningful benefits. They emphasize that Codex standards require ingredients to demonstrate suitability through either human milk composition or clinical benefits, making it critical to ensure sufficient amounts are present to achieve intended outcomes. One expert notes this allows for "justifiable effectiveness that does not vary across the industry."
Opposition to Minimum Requirements (5 experts): This group prioritizes upper safety limits over minimum efficacy thresholds. Key concerns include:
- Difficulty in defining minimum effective levels
- Upper safety limits are more important and should be driven by maximum levels in human breast milk
- Appropriate levels should be guided by human milk composition, though this is complex given wide variation
Context-Dependent Approach (5 experts): These experts advocate for case-by-case evaluation, distinguishing between:
- Ingredients with defined physiological roles and measurable outcomes (where minimums are justified)
- Ingredients supporting broader developmental trajectories or population-level benefits (where safety limits may be more relevant)
A common thread across positions is the importance of upper safety limits, with several experts suggesting these should not exceed the highest levels found in human milk without additional safety evidence. Multiple experts acknowledge the complexity of using human milk as a reference given its natural variation over time and between individuals.
Answer Explanations
- Yes—minimum effective level should be required for all optional ingredientsuser-641377The Codex standard also establishes criteria for what ingredients should be added to infant formula, with an ingredient needing to show suitability either through a reference to similar levels being present in human milk, or linked to clinical results that demonstrate a benefit (the benefit being bringing infant formula function closer to that of human milk). In both of those cases, it would be critical to make sure sufficient amounts of the ingredient are present in the formula.
- Context-dependent (please specify in comments)user-487133The need for a minimum effective level should depend on the intended function, strength of evidence, and biological mechanism of action. For ingredients with a defined physiological role and measurable functional outcome, establishing a minimum effective level is scientifically justified once safety is established. Conversely, for ingredients intended to support broader developmental trajectories or population-level outcomes analogous to breastfeeding, upper safety limits and total exposure may be more relevant than strict efficacy thresholds.
- Context-dependent (please specify in comments)user-801459A context-dependent approach is most appropriate. For some bioactive ingredients with defined mechanisms and measurable outcomes, establishing a minimum effective level is scientifically justified. For others, especially where function is multifactorial or population-level benefits are inferred from human milk composition, prioritizing safety and avoiding excessive dosing may be more appropriate than defining a strict efficacy threshold.
- No—presence at any level (guided by human milk composition and/or function) is sufficient if safety is establisheduser-685It is going to be very difficult to define minimum effective levels.
- Context-dependent (please specify in comments)user-804372I believe that both minimum and maximum levels should be recommended. The minimum should be the lowest level that was shown to be clinically efficacious for the outcomes of interest. In terms of the maximum, I think the highest level reported in human milk should not be exceeded without evidence demonstrating that higher concentrations are safe.
- No—presence at any level (guided by human milk composition and/or function) is sufficient if safety is establisheduser-519519We also consider that the upper safety limit is more important than lower efficacy limit. The upper safety limit should be driven the maximum levels in human breast milk and validated by suitable safety studies.
- No—presence at any level (guided by human milk composition and/or function) is sufficient if safety is establisheduser-457378I'd like to see option 2 and 3 combined. An upper safety limit is a fundamental necessity. Appropriate levels should be guided by human milk this is complex in itself given the wide variation in BM composition over time and between individuals.
- Yes—minimum effective level should be required for all optional ingredientsuser-113927A minimum effective allows for justifiable effectiveness that does not vary across the industry. Upper safety limits are important but importance will vary by bioactive
- Context-dependent (please specify in comments)user-808679I think the ingredients should be evaluated on a case-by-case basis. Not sure but a range may be more useful as some of these components may vary over time or based upon other factors. Need to understand variation in human milk and relate to exposure via infant formula.
- Context-dependent (please specify in comments)user-886637Should clearly state safety doses and limits (upper safety limit) and later we can measure efficacy to safety ratio